COMPOUND AND PHARMACEUTICAL COMPOSITION FOR TUMOR IMAGING AND TUMOR THERAPY
A compound represented by formula (I) is provided, wherein in formula (I), R1 and R2 each independently represents hydrogen, O—R3 or S—R4, at least one of R1 and R2 is O—R3 or S—R4, and R3 and R4 are independently a C1 to C10 alkyl group, such that the C1 to C10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of —OH, —NH2, halogen, ester, ether, and carboxylic acid, and M being a metal or a metal-containing compound. The compound represented by formula (I) is shown to have higher specificity to tumor cells, and is therefore suitable for carrying anti-cancer drugs and/or nuclear imaging agents.
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The present invention generally relates to a compound and a pharmaceutical composition, in particular, to a compound and a pharmaceutical composition with improved specificity and efficiency for tumor imaging and tumor therapy.
2. Description of Related ArtThere are a variety of cancer treatment methods available depending on the type and stage of cancer. In general, the treatments may involve the combination of chemotherapy, radiation therapy, hormone therapy, immunotherapy or surgery. The key to successful cancer treatment may require the identification of tumor through tumor imaging at an early stage, as well as targeted drug delivery during chemotherapy. Tumor imaging serves as the frontline in diagnosing cancer and allows us to trace and observe the efficacy of tumor therapy before and after the treatment. Nuclear imaging agents are conventionally used in tumor imaging for highlighting the existence and position of tumor. On the other hand, in order to eradicate cancer, anti-cancer drugs are commonly used to reduce the size of tumor and to prevent metastasis.
In tumor imaging and therapy, the specificity of the compound used in tumor imaging and tumor therapy is one of the most important factors that needs to be considered. For instance, compounds having high specificity for the tumor cells will provide good efficiency and accuracy in tumor imaging. Similarly, compounds having high specificity for the tumor cells will enable good efficacy of the anti-cancer drugs while reducing side effects during tumor treatment. In this regard, amino acid transporter system is found to be involved in improving the specificity of tumor imaging/therapy, as researchers have shown that the uptake of some amino acids are up-regulated in cancer cells. However, labeled amino acids are not widely applied in tumor imaging/therapy due to its high cost and complexity. Therefore, alternative compounds having improved specificity and efficiency for tumor imaging and therapy are desired.
SUMMARY OF THE INVENTIONAccordingly, the present invention provides a compound and a pharmaceutical composition that have improved specificity to tumor cells, and is suitable for carrying anti-cancer drugs and/or nuclear imaging agents.
The invention provides a compound represented by formula (I):
in formula (I), R1 and R2 each independently represents hydrogen, O—R3 or S—R4, wherein at least one of R1 and R7 is O—R3 or S—R4, and R3 and R4 are independently a C1 to C10 alkyl group, such that the C1 to C10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of —OH, —NH2, halogen, ester, ether, and carboxylic acid; and wherein M is a metal or a metal-containing compound.
In an embodiment of the invention, the metal or the metal-containing compound M is 99mTc, 117mSn, 188Re, 186Re, 90Y, 67Ga, 68Ga, 166Ho, 153Sm, 59Fe, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 187Re, 89Y, 69Ga, 153Pt, 27Al, 56Fe, 64Cu, 118Sn, 10B, 58Co, 79Se, 40Ca, 64Zn, 157Gd, or a combination thereof.
In an embodiment of the invention, one of R1 and R2 is hydrogen and the other one is S—R3.
In an embodiment of the invention, S—R3 is cysteine.
In an embodiment of the invention, the compound is further represented by formula (II) or formula (III):
wherein in formula (II) and formula (III), X is an anticancer drug, an antiviral drug, an antibacterial drug, or a combination thereof.
In an embodiment of the invention, the drug X is melphalan, chlorambucil, methotrexate, paclitaxel, metronidazole, doxorubicin, penciclovir, ganciclovir, acyclovir, anti-EGFR antibody, anti-VEGF antibody, anti-PDGF antibody, retinoic acid, RGD peptide, or octreotide.
In an embodiment of the invention, the compound of formula (I) is obtained by conjugating the metal or the metal-containing compound M to a compound represented by formula (IV),
wherein the compound represented by formula (IV) has two stereoisomeric forms and only one of the stereoisomeric form is used for conjugation to the metal or the metal-containing compound M.
In an embodiment of the invention, the two stereoisomeric forms of formula (IV) is represented by formula (IV-a) and formula (IV-b):
wherein only the stereoisomeric form represented by formula (IV-a) is used for conjugation to the metal or the metal-containing compound M.
The invention further provides a pharmaceutical composition for tumor imaging and/or tumor treatment. The pharmaceutical composition includes a pharmaceutically-acceptable carrier, and a compound represented by formula (I):
in formula (I), R1 and R2 each independently represents hydrogen, O—R3 or S—R4, wherein at least one of R1 and R2 is O—R3 or S—R4, and R3 and R4 are independently a C1 to C10 alkyl group, such that the C1 to C10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of —OH, —NH2, halogen, ester, ether, and carboxylic acid; and M is a metal or a metal-containing compound.
In an embodiment of the invention, the metal or the metal-containing compound M is 99mTc, 117mSn, 188Re, 186Re, 90Y, 67Ga, 68Ga, 166Ho, 153Sm, 59Fe, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 187Re, 89Y, 69Ga, 153Pt, 27Al, 56Fe, 64Cu, 118Sn, 10B, 58Co, 79Se, 40Ca, 64Zn, 157Gd, or a combination thereof.
In an embodiment of the invention, one of R1 and R2 is hydrogen and the other one is S—R3.
In an embodiment of the invention, S—R3 is cysteine.
In an embodiment of the invention, the compound is further represented by formula (II) or formula (III):
wherein in formula (II) and formula (III), X is an anticancer drug, an antiviral drug, an antibacterial drug, or a combination thereof.
In an embodiment of the invention, the drug X is melphalan, chlorambucil, methotrexate, paclitaxel, metronidazole, doxorubicin, penciclovir, ganciclovir, acyclovir, anti-EGFR antibody, anti-VEGF antibody, anti-PDGF antibody, retinoic acid, RGD peptide, or octreotide.
In an embodiment of the invention, the compound of formula (I) is obtained by conjugating the metal or the metal-containing compound M to a compound represented by formula (IV),
wherein the compound represented by formula (IV) has two stereoisomeric forms and only one of the stereoisomeric form is used for conjugation to the metal or the metal-containing compound M.
In an embodiment of the invention, the two stereoisomeric forms of formula (IV) is represented by formula (IV-a) and formula (IV-b):
wherein only the stereoisomeric form represented by formula (IV-a) is used for conjugation to the metal or the metal-containing compound M.
Based on the above, the compound and the pharmaceutical composition of the present invention have improved specificity to tumor cells, and is therefore suitable for carrying anti-cancer drugs and/or nuclear imaging agents.
In order to make the aforementioned features and advantages of the disclosure more comprehensible, embodiments accompanied with figures are described in detail below.
The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.
Reference will now be made in detail to the present preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used in the drawings and the description to refer to the same or like parts.
The present invention provides a compound with good specificity to tumor cells, and is therefore suitable for carrying anti-cancer drugs and/or nuclear imaging agents. In an embodiment of the invention, the compound may be considered as a metallic-succinate based conjugate. In another embodiment of the invention, the compound may be considered as a succinate-cysteine based conjugate. Nevertheless, it is important to recognize that the term “metallic-succinate based conjugate” or “succinate-cysteine based conjugate” is merely used to describe the structure of compounds in specific embodiments of the invention, but do not serve to limit the compound of the present invention to these specific structures.
In the present embodiment, a compound of the present invention is represented by formula (I):
The compound represented by formula (I) is for example, a metallic-succinate based conjugate. In formula (I), R1 and R2 each independently represents hydrogen, O—R3 or S—R4, wherein at least one of R1 and R2 is O—R3 or S—R4, and R3 and R4 are independently a C1 to C10 alkyl group, such that the C1 to C10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of —OH, —NH2, halogen, ester, ether, and carboxylic acid. Furthermore, M is a metal or a metal-containing compound.
More specifically, the metal or the metal-containing compounds M are for example radiolabeled compounds that may be used as nuclear imaging agents. For instance, in an embodiment of the invention, the metal or the metal-containing compound M is 99mTc, 117mSn, 188Re, 186Re, 90Y, 67Ga, 68Ga, 166Ho, 153Sm, 59Fe, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 187Re, 89Y, 69Ga, 153Pt, 27Al, 56Fe, 64Cu, 118Sn, 10B, 58Co, 79Se, 40Ca, 64Zn, 157Gd, or a combination thereof. However, the metal or the metal-containing compound M of the present invention is not particularly limited thereto, and can be any other metal or metal-containing compounds that are suitable for tumor imaging.
Furthermore, for the compound represented by formula (I), it is preferable that one of R1 and R2 is hydrogen and the other one is S—R3, wherein S—R3 is cysteine. Specific examples of such compounds of formula (I) may be further represented by formula (II) or formula (III) shown below.
In formula (II) and formula (III), X is an anticancer drug, an antiviral drug, an antibacterial drug, or a combination thereof, whereas the metal or the metal-containing compounds M are similar to that of formula (I) described above. The compounds of formula (II) and formula (III) are suitable for use in tumor therapy, wherein the compounds have a succinate-cysteine based structure that is conjugated with different types of drug X depending on the purpose of treatment. For example, the drug X that may be conjugated to the succinate-cysteine based structure are such as melphalan, chlorambucil, methotrexate, paclitaxel, metronidazole, doxorubicin, penciclovir, ganciclovir, acyclovir, anti-EGFR antibody, anti-VEGF antibody, anti-PDGF antibody, retinoic acid, RGD peptide, or octreotide. Other suitable drugs may also be conjugated to the succinate-cysteine based structure based on requirement.
In an embodiment of the invention, the compound of formula (I) is obtained by conjugating the metal or the metal-containing compound M to a compound represented by formula (IV).
The compound of formula (IV), is a succinic acid-cysteine (SAC) with a chemical name of 2-amino-3-[(1,2-dicarboxyethyl)sulfanyl] propionic acid. More specifically, the compound of formula (IV) (or the SAC compound) has two stereoisomeric forms, and in the present embodiment, only one of the stereoisomeric form is used for conjugation to the metal or the metal-containing compound M.
In the present embodiment, the two stereoisomeric forms of formula (IV) is represented by formula (IV-a) and formula (IV-b):
Furthermore, only the stereoisomeric form represented by formula (IV-a) is used for conjugation to the metal or the metal-containing compound M. In the present invention the compound represented by formula (IV-a) (herein abbreviated as SAC-A) was found to have higher radiolabeling purity than the other stereoisomeric form of formula (IV-b) (herein abbreviated as SAC-B). Therefore, the compound of SAC-A is more preferable than the other stereoisomers for use in tumor imaging and tumor therapy.
In the present embodiment, in order to obtain the compound represented by formula (I), the metal or the metal containing compound M is conjugated to the two carboxylic acid groups in the succinic acid-cysteine (SAC) compound of formula (IV). Although the compound of SAC-A is more preferable than the other stereoisomers for use in tumor imaging and tumor therapy, however, the other stereoisomers such as SAC-B or the mixture of the stereoisomers may still be used in tumor imaging and tumor therapy to achieve similar effects.
Furthermore, the succinic acid-cysteine (SAC) compound of formula (IV) is also suitable to be conjugated to the metal or the metal containing compound M and the drug X at the same time in order to obtain the compounds represented by formula (II) and formula (III) shown above. For example, the drug X may be reacted and attached through the amine portion of the cysteine in the SAC compound, or alternatively, be reacted and attached through the acid portion of the cysteine in the SAC compound. After attachment of the drug X to the SAC compound, the compound may be used in tumor therapy. For example, in tumors observed in neuroendocrine cancer, brain cancer, breast cancer, prostate cancer, colon cancer, lung cancer, liver cancer, pancreas cancer, gastric cancer, lymphoma and uterine tumor, cervical tumor, extremitas tumor, sarcoma, melanoma and many more.
Therefore, the SAC compound of the present invention may be suitable for conjugating to the metal or the metal containing compound M for use in tumor imaging, and suitable for conjugating to the drug X for tumor therapy (chemotherapy etc.) to obtain the compounds of the present invention. It is worth mentioning that the SAC compound (represented by formula (IV)) was set forth as a specific example of forming the compound represented by formula (I) of the present invention. However, the present invention is not limited thereto, and those compounds structurally similar to the compound of formula (I) may be used.
In addition, in another embodiment of the invention, the compound represented by formula (I) may be used in a pharmaceutical composition for tumor imaging and/or tumor treatment. For example, the pharmaceutical composition may comprise a pharmaceutically-acceptable carrier in combination with the compound represented by formula (I) described above. The pharmaceutically-acceptable carrier used may include but are not limited to water, phosphate buffered saline, alcohol, glycerol, chitosan, alginate, chondroitin, vitamin E, mineral oil, dimethyl sulfoxide (DMSO), cyclodextrin, polylactic acid, or a combination of the above. The pharmaceutically-acceptable carrier may be appropriately selected based on the requirements of tumor imaging and/or tumor treatment.
To prove that the compounds of the present invention are suitable for canying anti-cancer drugs and/or nuclear imaging agents, the compounds of the present invention are synthesized and tested by using the method described in the following examples.
EXAMPLE 1 Synthesis of Succinic Acid-Cysteine (SAC)The succinic acid-cysteine (SAC) or the compound represented by formula (IV) is synthesized using the method described in scheme 1 below.
As shown in scheme 1, the SAC compound of example 1 is synthesized by the following process. Maleic acid (23.2 g, 0.2 mol) was added to a solution of L-cysteine (24.2 g, 0.2 mol) in water (1 L). The reaction mixture was stirred at room temperature for 24 hours, and acetone (3 L) was added thereto. The precipitate was collected by filtration and recrystallized from methanol to give a diastereoisomeric mixture (SAC-A+SAC-B; 32.9 g, 70% yield). The structure of the diastereoisomeric SAC compound was confirmed by 1H-NMR and 13C-NMR as shown in
Specifically,
The SAC compounds synthesized in the above example may be used for carrying anti-cancer drugs and/or nuclear imaging agents. As a specific example, the synthesis of the metallic-succinate based conjugates of 99mTc-SAC, and 68Ga-SAC are described below.
Synthesis of 99mTc-SAC and 68Ga-SAC
For 99mTc-labeling, the diastereoisomeric SAC compound (5 mg) was dissolved in 0.2 mL of water, and Tin (II) chloride (0.1 mg) dissolved in 0.1 mL water and sodium pertechnetate Na99mTcO4 (1 mCi) was directly added to the SAC compound solution. Thereafter, the 99mTc-SAC compound is obtained.
For 68Ga-labelling, the diastereoisomeric SAC compound (5 mg) was dissolved in 0.2 mL of water, and 68GaCl3 (5 mCi) was directly added to the SAC compound solution, followed by heating at 70° C. for 10 minutes. Thereafter, the 68Ga-SAC compound is obtained.
Radio-thin layer chromatography using three systems (acetone, saline, 1M NH4Cl/MeOH (4:1) was used to analyze the radiochemical purity of 99mTc-SAC and 68Ga-SAC. Radiochemical purity of 99mTc-SAC and 68Ga-SAC analyzed by these systems were greater than 96%. The results above prove that the SAC compound is suitable for carrying nuclear imaging agents, and the 99mTc-SAC and 68Ga-SAC compounds may correspond to the compound represented by formula (I) as described in the embodiments of the present invention.
EXAMPLE 2 In-vitro Cellular Uptake StudiesTo verify that the compounds of the present vention are suitable for carrying anti-cancer drugs to targeted sites, the following in-vitro cellular uptake studies were performed.
Breast cancer cells (13762) from RBA CRL-1747 rat breast cancer cell line (American Type Culture Collection, Rockville, Md.) were used. The cancer cells were plated onto 12-well tissue culture plates at a concentration of 50,000 cells per well for carrying out the uptake studies. The cells were cultured in Eagle's MEM with Earle's BSS (90%) and fetal bovine serum (10%) under standard culture conditions (37° C., 95% humidified air and 5% CO2). After seeding, the cells were incubated at 37° C. for 48 hours to allow for cell attachment and growth. After reaching approximately 70% confluency of cells, the cells are ready for use in the cellular uptake experiments.
Specifically, upon reaching 70% cell confluency, the growth media were aspirated and the cells were washed twice with phosphate buffered saline (PBS). Serum-free media and 99mTc-SAC obtained in Example 1 were added to the cells for performing the cellular uptake experiment. Similarly, 99mTc-succinate was used as a control and were added to the cells with the serum-free media. The cells with the added test compounds were incubated for 60 minutes with 5% CO2 and 95% air at 37° C. To ascertain the subcellular distribution of 99° Tc-SAC, cell fraction assays (cytosol and nucleus) were performed at 60 min post-incubation. The cells were harvested by washing twice with phosphate-buffered saline (PBS) (0.5 ml) and detached using trypsin-EDTA (0.2 ml) for 5 minutes. After 5 minutes of incubation, PBS (0.5 ml) was added, and the total volume was transferred to a test tube for evaluation.
The radioactivity of the test compounds was counted using a Packard Cobra gamma counter (Downers Grover, Ill.). Data points represented an average of three measurements that were calculated as a percent uptake per number of viable cells. The results of the cellular uptake studies are presented in
As noted above, the SAC compound (represented by formula (IV) may contain the stereoisomers SAC-A (formula (IV-a)) and SAC-B (formula (IV-b)). In the following example, the stereoisomers SAC-A and SAC-B were separated and purified, and their radiolabeling purity was compared.
Separation of the Succinic Acid-Cysteine (SAC) Compound StereoisomersThe diastereoisomeric SAC compound prepared in Example 1 was used for separation. Specifically, 70mg of the diastereoisomeric SAC compound was subjected to chromatography on Dowex 50 W resin [200-400 mesh, 1.5×90 cm, buffered with a pH 2.50 ammonia-formate buffer and eluted with a pH 2.70 buffer (5 mL fractions)]. Fractions which showed peaks at tR 18.5 and 19.5 minutes on HPLC were respectively combined and desalted using Dowex 50 W to give the stereoisomers SAC-A (10 mg) and SAC-B (5 mg) respectively.
The compound SAC-A is the stereoisomer of interest, and its 1 H NMR, 13C NMR, and COSY spectrums are presented in
Radiolabeling of SAC-A and SAC-B with 99mTC
For 99mTc-labeling, the SAC-A compound (5 mg) and the SAC-B compound (5 mg) were separately dissolved in 0.2 mL of water, and Tin (II) chloride (0.1 mg dissolved in 0.1 mL water) was added thereto at room temperature. Next, sodium pertechnetate Na99mTcO4 (5 mCi) was directly added to the above solution. Thereafter, the 99mTc-SAC-A and the 99mTc-SAC-B compounds are obtained.
The radiochemical purity of the 99mTc-SAC-A and the 99mTc-SAC-B compounds were determined by radio-thin layer chromatography (ITLC, SG, Gelman Sciences, Ann Arbor, Mich.). The results of the radiochemical purity are presented in
It should be noted that the SAC compound containing the two stereoisomeric forms can possibly be used for providing high radiochemical purity. However, from the experiments above, it can be known that the high radio-chemical yield of the SAC compound is mostly attributed to the presence of the SAC-A stereoisomer (compound with formula (IV-a)). Since the amount ratio of the SAC-A stereoisomer to the SAC-B stereoisomer in the SAC compound may be varied and shifted in different samples, a high radiochemical purity cannot be always confirmed. As such, by specifically separating out the SAC-A stereoisomeric form, a high radiochemical purity and radiolabeling efficiency can be guaranteed.
Based on the above, the compound represented by formula (I) of the invention was shown to have improved specificity to tumor cells (cellular uptake to nucleus), and is therefore suitable for carrying anti-cancer drugs and/or nuclear imaging agents. Moreover, it is preferable that the compound of formula (I) is obtained by conjugating the metal or the metal-containing compound M to a compound represented by formula (IV), wherein only one one of the stereoisomeric forms of foi (IV) is used for conjugation to the metal or the metal-containing compound M. As such, when one of the stereoisomeric form (SAC-A) is used for conjugation, the resulting compound can have a higher radiolabeling stability, and is therefore more desirable for use in tumor imaging and tumor therapy.
It will be apparent to those skilled in the art that various modifications and variations can be made to the structure of the present invention without departing from the scope or spirit of the invention. In view of the foregoing, it is intended that the present invention cover modifications and variations of this invention provided they fall within the scope of the following claims and their equivalents.
Claims
1. A compound represented by formula (I):
- in formula (I), R1 and R2 each independently represents hydrogen, O—R3 or S—R4, wherein at least one of R1 and R7 is O—R3 or S—R4, and R3 and R4 are independently a C1 to C10 alkyl group, such that the C1 to C10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of —OH, —NH2, halogen, ester, ether, and carboxylic acid; and
- wherein M is a metal or a metal-containing compound.
2. The compound according to claim 1, wherein the metal or the metal-containing compound M is 99mTc, 117mSn, 188Re, 186Re, 90Y, 67Ga, 68Ga, 166Ho, 153Sm, 59Fe, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 187Re, 89Y, 69Ga, 153Pt, 27Al, 56Fe, 64Cu, 118Sn, 10B, 58Co, 79Se, 40Ca, 64Zn, 157Gd, or a combination thereof.
3. The compound according to claim 1, wherein one of R1 and R2 is hydrogen and the other one is S—R3.
4. The compound according to claim 3, wherein S—R3 s cysteine.
5. The compound according to claim 1, wherein the compound is further represented by formula (II) or formula (III):
- wherein in formula (II) and formula (III), X is an anticancer drug, an antiviral drug, an antibacterial drug, or a combination thereof.
6. The compound according to claim 5, wherein the drug X is melphalan, chlorambucil, methotrexate, paclitaxel, metronidazole, doxorubicin, penciclovir, ganciclovir, acyclovir, anti-EGFR antibody, anti-VEGF antibody, anti-PDGF antibody, retinoic acid, RGD peptide, or octreotide.
7. The compound according to claim 1, wherein the compound of formula (I) is obtained by conjugating the metal or the metal-containing compound M to a compound represented by formula (IV),
- wherein the compound represented by formula (IV) has two stereoisomeric forms and only one of the stereoisomeric form is used for conjugation to the metal or the metal-containing compound M.
8. The compound according to claim 7, wherein the two stereoisomeric forms of formula (IV) is represented by formula (IV-a) and formula (IV-b):
- wherein only the stereoisomeric form represented by formula (IV-a) is used for conjugation to the metal or the metal-containing compound M.
9. A pharmaceutical composition for tumor imaging and/or tumor therapy, comprising:
- a pharmaceutically-acceptable carrier; and
- a compound represented by formula (I):
- in formula (I), R1 and R2 each independently represents hydrogen, O—R3 or S—R4, wherein at least one of R1 and R2 is O—R3 or S—R4, and R3 and R4 are independently a C1 to C10 alkyl group, such that the C1 to C10 alkyl group is non-substituted or substituted with at least one selected from the group consisting of —OH, —NH2, halogen, ester, ether, and carboxylic acid; and M is a metal or a metal-containing compound.
10. The pharmaceutical composition according claim 9, wherein the metal or the metal-containing compound M is 99mTc, 117mSn, 188Re, 186Re, 90Y, 67Ga, 68Ga, 166Ho, 153Sm, 59Fe, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 187Re, 89Y, 69Ga, 153Pt, 27Al, 56Fe, 64Cu, 118Sn, 10B, 58Co, 79Se, 40Ca, 64Zn, 157Gd, or a combination thereof.
11. The pharmaceutical composition according to claim 9, wherein one of R1 and R2 is hydrogen and the other one is S—R3.
12. The pharmaceutical composition according to claim 11, wherein S—R3 is cysteine.
13. The pharmaceutical composition according to claim 9, wherein the compound is further represented by formula (II) or formula (III):
- wherein in formula (II) and formula (III), X is an anticancer drug, an antiviral drug, an antibacterial drug, or a combination thereof
14. The pharmaceutical composition according to claim 13, wherein the drug X is melphalan, chlorambucil, methotrexate, paclitaxel, metronidazole, doxorubicin, penciclovir, ganciclovir, acyclovir, anti-EGFR antibody, anti-VEGF antibody, anti-PDGF antibody, retinoic acid, RGD peptide, or octreotide.
15. The pharmaceutical composition according to claim 9, wherein the compound of formula (I) is obtained by conjugating the metal or the metal-containing compound M to a compound represented by formula (IV),
- wherein the compound represented by formula (IV) has two stereoisomeric forms and only one of the stereoisomeric form is used for conjugation to the metal or the metal-containing compound M.
16. The pharmaceutical composition according to claim 15, wherein the two stereoisomeric forms of formula (IV) is represented by formula (IV-a) and formula (IV-b):
- wherein only the stereoisomeric fonn represented by formula (IV-a) is used for conjugation to the metal or the metal-containing compound M.
Type: Application
Filed: Jan 9, 2017
Publication Date: Jul 12, 2018
Applicant: SeeCure Taiwan Co., Ltd. (Kaohsiung City)
Inventors: Wei-Chung Chang (Kaohsiung City), Kun-Hsin Lee (Kaohsiung City), Kai-Chi Chang (Kaohsiung City), Ping-Fan Chen (Kaohsiung City), Min-Huei Huang (Kaohsiung City), Hung-Yuan Huang (Kaohsiung City), Ning Tsao (Kaohsiung City)
Application Number: 15/401,111
