THERAPY DOSSIER · th-7a827944cb71

17-DMAG (17-dimethylamino-ethylamino-17-demethoxygeldanamycin), an Hsp90 inhibitor

Drug · Heat shock protein HSP90 inhibitor (INHIBITOR); anticancer mechanism not fully elucidated, may act via generation of reactive oxygen species

Not approved Suggest a correction

Evidence & regulatory context

Mechanism: Heat shock protein HSP90 inhibitor (INHIBITOR); anticancer mechanism not fully elucidated, may act via generation of reactive oxygen species
Target: CHEMBL2095165
Injury models: Endotoxin/LPS
Reported indication: Not recorded
First approval: Not recorded
Development stage: In trials, not approved
ChEMBL record: CHEMBL383824 ↗
ChEMBL max phase: 2 / 4 (development scale, not regulatory approval)
Synonyms: Alvespimycin; Alvespimicina; NSC-707545; 17-DMAG HCl; KOS-1022; BMS-826476
Note: Not recorded

Clinical trials 7

0 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT00780000 ↗PHASE2terminated

Phase 2 Trial of Intravenous Alvespimycin (KOS-1022) in Her2 Positive Breast Cancer

Breast Cancer

Enrolment: 4 · Results not recorded

NCT00089271 ↗PHASE1completed

Phase I Study Of 17-DMAG (NSC 707545) In Patients With Advanced Solid Tumors

Lymphoma (multiple subtypes) · Unspecified Adult Solid Tumor

Enrolment: 60 · Results not recorded

NCT00089362 ↗PHASE1completed

Phase 1 Study of 17-DMAG (NSC 707545) in Patients With Solid Tumors

Solid tumours (breast, colon, renal, melanoma, head and neck)

Enrolment: 30 · Results not recorded

NCT00088868 ↗PHASE1completed

Phase I Study Of 17DMAG With Evaluation Of Hsp90 Client Proteins In Subjects With Solid Tumors And Lymphomas

Lymphoma · Small Intestine Cancer · Unspecified Adult Solid Tumor

Enrolment: 40 · Results not recorded

NCT00248521 ↗PHASE1unknown

Cancer Research UK Phase I Trial of 17-DMAG Once Weekly Infusion in Advanced Solid Tumors

Unspecified Adult Solid Tumor

Enrolment: 35 · Results not recorded

NCT01126502 ↗PHASE1terminated

Phase I Study of the Hsp90 Inhibitor 17-DMAG (Alvespimycin) in Relapsed CLL/SLL and B-PLL

B-cell Chronic Lymphocytic Leukemia · Prolymphocytic Leukemia · Recurrent Small Lymphocytic Lymphoma · Refractory Chronic Lymphocytic Leukemia

Enrolment: 30 · Results not recorded

NCT00803556 ↗PHASE1completed

Phase 1 Trial of Intravenous Alvespimycin (KOS-1022) With Trastuzumab With or Without Paclitaxel

Solid Tumor · Breast Cancer

Enrolment: 29 · Results not recorded

Preclinical evidence 1

1 studies reported at therapy level; 1 evidence entries itemised.

PMID 22105779 ↗2012Reported benefit

Inhibition of heat shock protein (molecular weight 90 kDa) attenuates proinflammatory cytokines and prevents lipopolysaccharide-induced liver injury in mice.

MouseEndotoxin/LPSC57BL/6Female and maleIntraperitoneal2.5, 5 or 30 mg/kg body weightAdministered with LPS; animals sacrificed at 2 or 18 hours

Model: Lipopolysaccharide-induced acute liver injury: 0.5 mg/kg body weight LPS (E. coli 0111:B4) in 0.1 mL intraperitoneally, with saline controls

17-DMAG significantly reduced LPS-induced serum alanine aminotransferase at all three doses independent of dose. Hepatic and serum TNF-alpha fell at 2.5 and 5 mg/kg and interleukin-6 at 5 mg/kg. HSF1 DNA binding and hsp70 rose dose-dependently, CD14 mRNA and NF-kappaB DNA binding fell without chang…

Extraction: extract · Supplied extraction confidence: 0.85. Machine-extracted fields require source verification.

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