Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Abstract: Disclosed herein are compounds and methods for the inhibition of the RNF1 or RNF2 subunit of polycomb repressive complex 1 (PRC1) for the treatment of metastatic cancer, such as metastatic castration-resistant prostate cancer. The inhibitors can be combined with checkpoint inhibitors such as PD-1 inhibitors, PD-L 1 inhibitors, or CTLA-4 inhibitors.

Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: The present disclosure describes methods of treatment (e.g., combination treatment) by ferroptotic induction, as well as compositions and dosing regimens that are part of such methods. Surprisingly, it is presently found that delaying administration of a ferroptosis-inducing agent until after starting hormone therapy results in enhanced ferroptotic induction in a subject. Thus, in certain embodiments, combination therapies are presented herein that include multiple administration steps whereby a ferroptosis-inducing agent is administered some time after hormone therapy has begun.

Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Abstract: Using an RT-PCR platform, detection of gene transcripts highly expressed in prostate tissue and expressed in peripheral blood mononuclear cells (PBMC) from patients with mCRPC can provide a more reliable and robust prediction of poor overall survival than that of CTC enumeration in mCRPC. Disclosed is the identification of five genes, KLK3, KLK2, HOXB13, GHRL2 and FOXA1, the detection of two (2) or more transcripts of which predicts overall poor survival. The test is performed on blood samples that have been collected in collection tubes that stabilize intracellular RNA, require minimal on-site processing and can be easily stored and shipped for subsequent extraction of total RNA from whole blood for RT-PCR.

Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: Using an RT-PCR platform, detection of gene transcripts highly expressed in prostate tissue and expressed in peripheral blood mononuclear cells (PBMC) from patients with mCRPC can provide a more reliable and robust prediction of poor overall survival than that of CTC enumeration in mCRPC. Disclosed is the identification of five genes, KLK3, KLK2, HOXB13, GHRL2 and FOXA1, the detection of two (2) or more transcripts of which predicts overall poor survival. The test is performed on blood samples that have been collected in collection tubes that stabilize intracellular RNA, require minimal on-site processing and can be easily stored and shipped for subsequent extraction of total RNA from whole blood for RT-PCR.

Abstract: The present invention provides analog and derivative compounds of (S,S,R)-(?)-actinonin and methods of asymmetric synthesis thereof having a structure: where R1 is hydrogen, C(O)R6 or R1 in combination with N is 2-oxomorpholine, R2 is hydrogen, methyl, CH2CH(CH3)2, (CH2)2CH3, CH(CH3)2, (CH2)3CH3, (CH2)4NH2, (CH2)3CO2H, phenyl, 3,4-dichlorophenyl, biphenyl, benzyl, 4-hydroxybenzyl, piperidine, N-Boc-4-piperidine, CH2-(N-Boc-4-piperidine), 4-tetrahydropyran, CH2-4-tetrahydropyran, 3-methyl indolyl, 2-naphthyl, 3-pyridyl, 4-pyridyl, 3-thienyl, R3 is R2 or C3-8alkyl, R4 is C1-3alkyl, R5 is NH2, OH, NHOH, NHOCH3, N(CH3)OH, N(CH3)OCH3, NHCH2CH3, NH(CH2CH3), NHCH2(2,4-(OCH3)2Ph, NHCH2(4-NO2)Ph, NHN(CH3)2, proline, or 2-hydroxymethyl pyrrolidine and R6 is an optionally substituted or halogenated alkyl, aryl, heteroalkyl or heteroaryl amine where R6 further comprising a cyclic or bicyclic structure.

Abstract: The present invention provides methods for the asymmetric synthesis of (S,S,R)-(?)-actinonin and its analogs and the compounds thereby synthesized having a structural formula: where R1 is an optionally substituted or halogenated alkyl, aryl, heteroalkyl or heteroaryl amine, said R1 further comprising a cyclic or bicyclic structure; R2 is methyl, CH2CH3, (CH2)2CH3, C(CH3)3, phenyl, 3,4-dichlorophenyl, biphenyl, benzyl, 4-hydroxybenzyl, piperidine, N-Boc-4-piperidine, CH2-(N-Boc-4-piperidine), 4-tetrahydropyran, CH2-4-tetrahydropyran, 3-methyl indolyl, 2-naphthyl, 3-pyridyl, 4-pyridyl, 3-thienyl; R3 is R2 or C3-8alkyl, R4 is C1-3alkyl; and R5 is NH2, OH, NHOH, NHOCH3, N(CH3)OH, N(CH3)OCH3, NHCH2CH3, NH(CH2CH3), NHCH2(2,4-(OCH3)2Ph, NHCH2(4-NO2)Ph, NHN(CH3)2, proline, or 2-hydroxymethyl pyrrolidine.

Abstract: The present invention provides methods for the asymmetric synthesis of (S,S,R)-(−)-actinonin and its analogs and the compounds thereby synthesized having a structural formula: 1

Abstract: The present invention provides methods for the asymmetric synthesis of (S,S,R)-(−)-actinonin and its analogs and the compounds thereby synthesized having a structural formula: where R1 is an optionally substituted or halogenated alkyl, aryl, heteroalkyl or heteroaryl amine, said R1 further comprising a cyclic or bicyclic structure; R2 is methyl, CH2CH3, (CH2)2CH3, C(CH3)3, phenyl, 3,4-dichiorophenyl, biphenyl, benzyl, 4-hydroxybenzyl, piperidine, N-Boc-4-piperidine, CH2-(N-Boc-4-piperidine), 4-tetrahydropyran, CH2-4-tetrahydropyran, 3-methyl indolyl, 2-naphthyl, 3-pyridyl, 4-pyridyl, 3-thienyl; R3 is R2 or C3-8alkyl, R4 is C1-3alkyl; and R5 is NH2, OH, NHOH, NHOCH3, N(CH3)OH, N(CH3)OCH3, NHCH2CH3, NH(CH2CH3), NHCH2(2,4-(OCH3)2Ph, NHCH2(4-NO2)Ph, NHN(CH3)2, proline, or 2-hydroxymethyl pyrrolidine.

Abstract: The present invention provides a method of synthesizing a compound having the structure: as well as other related glycoconjugates useful as vaccines for inducing antibodies to epithelial cancer cells in an adjuvant therapy therefore, and in a method for preventing recurrence of epithelial cancer. The present invention also provides a vaccine comprising an amount of the compound described above effective to prevent the recurrence of cancer in a subject.

Abstract: The present invention provides methods for the asymmetric synthesis of (S,S,R)-(−)-actinonin and its analogs and the compounds thereby synthesized having a structural formula: 1