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Details

Stereochemistry ACHIRAL
Molecular Formula C22H30N6O2S
Molecular Weight 442.5795
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CUDC-305

SMILES

CC(C)(C)CNCCn1c2cc[nH]c(=N)c2nc1Sc3cc4c(cc3N(C)C)OCO4

InChI

InChIKey=RVJIQAYFTOPTKK-UHFFFAOYSA-N
InChI=1S/C22H30N6O2S/c1-22(2,3)12-24-8-9-28-14-6-7-25-20(23)19(14)26-21(28)31-18-11-17-16(29-13-30-17)10-15(18)27(4)5/h6-7,10-11,24H,8-9,12-13H2,1-5H3,(H2,23,25)

HIDE SMILES / InChI

Molecular Formula C22H30N6O2S
Molecular Weight 442.5795
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19509149

CUDC-305, is a novel heat shock protein 90 (HSP90) inhibitor with strong affinity for HSP90 alpha/beta, high oral bioavailability and potent anti-proliferative activity against a broad range of cancer cell lines (with a mean IC50 of 220 nmol/L), including many non-small cell lung cancer (NSCLC) cell lines which are resistant to standard-of-care (SOC) agents. In both laboratory and animal testing, CUDC-305 demonstrated high potency in vitro and/or in vivo across a wide range of cancers. Most notably, Curis scientists observed complete tumor regression following oral administration of CUDC-305 in a mouse xenograft model of acute myelogenous leukemia (AML). Tumor regression has also been observed after treatment of CUDC-305 in mouse xenograft models of breast, non-small cell lung, gastric cancer and glioblastoma brain cancers. In this preclinical testing, the compound also demonstrated an ability to effectively cross the blood brain barrier, and demonstrated an ability to extend survival in an intracranial glioblastoma model. Early stage toxicity studies suggest that CUDC-305 appears to have a better therapeutic window than several leading Hsp90 inhibitors in clinical development.

CNS Activity

Curator's Comment:: CUDC-305 can cross blood-brain barrier and reach therapeutic levels in brain tissue.

Approval Year

PubMed

PubMed

TitleDatePubMed
Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer.
2009 Dec
CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy.
2009 Jun 15
Patents

Sample Use Guides

Gelatin capsules of 2 dosage strengths (25 mg or 100 mg) The maximum dose will depend on the number of dose levels necessary to determine the MTD. CUDC-305 will be administered orally to sequential escalating dose cohorts, as an every-other-day schedule.
Route of Administration: Oral
CUDC-305 strongly bind to cancer-derived HSP90 complex with an IC50 of 61.2 nmol/L in H1975 and 74.2 nmol/L in H1993, respectively. 1 umol/L CUDC-305 reduced the levels of phospho-MET as well as total MET in H1993 and H1975 NSCLC cells
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:48:06 UTC 2021
Edited
by admin
on Sat Jun 26 03:48:06 UTC 2021
Record UNII
0V278OKN9G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CUDC-305
Common Name English
1H-IMIDAZO(4,5-C)PYRIDINE-1-ETHANAMINE, 4-AMINO-2-((6-(DIMETHYLAMINO)-1,3-BENZODIOXOL-5-YL)THIO)-N-(2,2-DIMETHYLPROPYL)-
Systematic Name English
2-((6-(DIMETHYLAMINO)BENZO(D)(1,3)DIOXOL-5-YL)THIO)-1-(2-(NEOPENTYLAMINO)ETHYL)-1H-IMIDAZO(4,5-C)PYRIDIN-4-AMINE
Systematic Name English
Hsp90 Inhibitor Debio 0932
Common Name English
CUDC305 (HSP90 INHIBITOR)
Common Name English
DEBIO-0932
Code English
Code System Code Type Description
MANUFACTURER PRODUCT INFORMATION
CUDC-305
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY Catalog No. A12648: CUDC-305 (DEBIO-0932)Quick Overview: Debio 0932 is a novel heat shock protein 90 (HSP90) inhibitor with strong affinity for HSP90 alpha/beta, high oral bioavailability and potent anti-proliferative activity against a broad range of cancer cell lines (with a mean IC50 of 220 nmol/L), including many non-small cell lung cancer (NSCLC) cell lines which are resistant to standard-of-care (SOC) agents.
PUBCHEM
44156921
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
DEBIO-0932
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY Biological Activity of Debio 0932:Debio 0932 (CUDC-305) is a novel heat shock protein 90 (HSP90) inhibitor trong affinity for HSP90 alpha/beta, high oral bioavailability and potent anti-proliferative activity against a broad range of cancer cell lines (with a mean IC50 of 220 nmol/L).target: HSP90IC50: 220 nmol/Lin vitro: H1993 and H1975 NSCLC cells were incubated with 1 .MU.mol/L CUDC-305 for 7 hours and then cultured in compound-free medium for an additional 0, 17, or 24 hours, respectively, before being analyzed by Western blotin vivo: CUDC-305 was delivered through oral gavage on an every-other-day (once every two days) dosing schedule at various doses up to 160 mg/kg-its maximum tolerated dose in nude mice. In survival studies in Balb/C nude mice, the highest dose was reduced to 120 mg/kg as a result of the compromised animal condition due to lung and brain tumor implantation surgeries.
FDA UNII
0V278OKN9G
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY
NCI_THESAURUS
C92572
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY NCIT
EPA CompTox
1061318-81-7
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY
CAS
1061318-81-7
Created by admin on Sat Jun 26 03:48:06 UTC 2021 , Edited by admin on Sat Jun 26 03:48:06 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
NCI Drug Dictionary: debio-0932 An orally active and small molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor Debio 0932 specifically blocks Hsp90, thereby inhibiting its chaperone function and promoting the degradation of its client proteins, many of which are oncogenic signaling proteins involved in tumor cell proliferation and survival. This may lead to an inhibition of tumor cell proliferation. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stabilization and degradation of many oncogenic signaling proteins. Check for active clinical trials using this agent. (NCI Thesaurus)
ACTIVE MOIETY
Originator: Curis; Developer: Curis, Debiopharm; Class: 2 ring heterocyclic compound, Antineoplastic, Benzodioxole, Imidazole, Pyridine, Small molecule; Mechanism of Action: HSP90 heat-shock protein inhibitor; Available For Licensing: Yes for Cancer; Highest Development Phases: Phase I for Cancer, Discontinued for Lymphoma, Non-small cell lung cancer, Renal cancer, Solid tumours; Most Recent Events: 19 Jun 2015 CUDC 305 is available for licensing as of 19 Jun 2015. http://www.curis.com/, 11 May 2015 Phase-I clinical trials in Cancer in USA (PO), 01 Feb 2015 Curis re-acquires CUDC 305 from Debiopharm