Abstract: This disclosure describes embodiments of selective and potent CDK 4/6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. As described herein, compounds of the present approach comprise substituted pyridinylpiperazine-pyrrolopyrimidine compounds having a fatty acid moiety. The compounds described herein may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and/or amelioration of cancer.

Abstract: This disclosure describes embodiments of selective and potent CDK 4/6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. As described herein, compounds of the present approach comprise substituted pyridinylpiper-azine-pyrrolopyrimidine compounds having a fatty acid moiety. The compounds described herein may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and/or amelioration of cancer.

Abstract: High ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anti-cancer therapy, especially for preventing tumor progression. A mitochondrial-related gene signature for metastasis is described, which features the gamma-subunit of the mitochondrial ATP-synthase (ATP5F1C). Knock-down of ATP5F1C expression significantly reduces ATP-production, 3D anchorage-independent growth and cell migration. Administration of the Bedaquiline, or a Bedaquiline derivative with a fatty acid moiety, down-regulates ATP5F1C expression in vitro and prevents spontaneous metastasis in vivo. Mitochondrial ATP5F1C is a promising new biomarker and molecular target for future drug development, for the prevention of metastatic disease progression.

Abstract: This disclosure describes embodiments of selective and potent CDK 4/6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. As described herein, compounds of the present approach comprise substituted pyridinylpiper-azine-pyrrolopyrimidine compounds having a fatty acid moiety. The compounds described herein may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and/or amelioration of cancer.

Abstract: Disclosed are 9-amino-doxycycline derivatives that target cancer stem cells and inhibit cancer metastasis. These compounds selectively target CSCs, potently inhibit tumor cell metastasis in vivo, with little or no toxicity, and minimize the risk of driving antibiotic resistance. In one embodiment, a 14 carbon fatty acid moiety is covalently attached to the free amino group of 9-amino-doxycycline. The resulting “Doxy-Myr” conjugate is over 5-fold more potent than doxycycline for inhibiting the anchorage-independent growth of MCF7 CSCs. Doxy-Myr did not affect the viability of the total MCF7 cancer cell population or normal fibroblasts grown as 2D-monolayers, showing remarkable selectivity for CSCs. Doxy-Myr did not show antibiotic activity, against Escherichia coli and Staphylococcus aureus. Conjugates having either longer (16 carbon; palmitic acid) or shorter (12 carbon; lauric acid) fatty acid chain lengths had similar activity.

Abstract: The disclosure describes selective and potent CDK 4/6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. A class of the CDK 4/6 inhibitors relates to substituted pyridopyrimidines compounds having a fatty acid moiety, and are namely derivatives of Palbociclib of general formula [2A], wherein R1 is hydrogen, aryl, alkyl, alkoxy, cycloalkyl, or heterocyclyl; R2 is hydrogen, halogen, alkyl, acyl, cycloalkyl, alkoxy, alkoxy alkyl, haloalkyl, hydroxy alkyl, alkenyl, alkynyl, nitrile, or nitro; R3 is hydrogen, halogen, alkyl, haloalkyl, hydroxy alkyl, or cycloalkyl; and n is an integer from 9 to 20. These compounds may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and/or amelioration of cancer.

Abstract: This disclosure describes selective and potent CDK 4/6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. This class of anti-cancer CDK 4/6 inhibitors are substituted pyrrolopyrimidine compounds of formula IA, having a fatty acid moiety. These compounds may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and/or amelioration of cancer.

Abstract: A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(?O)2; where Ra is H, C1-C4 alkyl or CH3C(?O); R5 is independently selected from H or methyl; E is —C(?O)—, —S(?O)m—, —NR5S(?O)m—, —NR5C(?O)—, —OC(?O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or hetorocycle; m is independently 0, 1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

Abstract: A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(?O)2; where Ra is H, C1-C4 alkyl or CH3C(?O); R5 is independently selected from H or methyl; E is —C(?O)—, —S(?O)m—, —NR5S(?O)m—, —NR5C(?O)—, —OC(?O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

Abstract: A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(?O)2; where Ra is H, C1-C4 alkyl or CH3C(?O); R5 is independently selected from H or methyl; E is —C(?O)—, —S(?O)m—, —NR5S(?O)m—, —NR5C(?O)—, —OC(?O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.