WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205737
Description: Debio 0932, also known as 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. Debio 0932 potently inhibits tumour growth in subcutaneous xenograft models of a number of solid and haematological malignancies, including models of NSCLC which harbour mutations conferring acquired or primary erlotinib resistance.
MedKoo Cat#: 205737
Name: Debio-0932 (CUDC305)
Chemical Formula: C22H30N6O2S
Exact Mass: 442.21509
Molecular Weight: 442.5776
Elemental Analysis: C, 59.70; H, 6.83; N, 18.99; O, 7.23; S, 7.25
Synonym: Debio0932; Debio-0932; Debio 0932; CUDC305; CUDC-305; CUDC 305.
IUPAC/Chemical Name: 2-((6-(dimethylamino)benzo[d][1,3]dioxol-5-yl)thio)-1-(2-(neopentylamino)ethyl)-1H-imidazo[4,5-c]pyridin-4-amine
InChi Key: PFYLLYYLCPZDMP-LBPRGKRZSA-N
InChi Code: InChI=1S/C18H18Cl2N6OS/c1-22-18-23-5-4-14(26-18)17-24-9-15(28-17)16(27)25-12(8-21)6-10-2-3-11(19)7-13(10)20/h2-5,7,9,12H,6,8,21H2,1H3,(H,25,27)(H,22,23,26)/t12-/m0/s1
SMILES Code: O=C(C1=CN=C(C2=NC(NC)=NC=C2)S1)N[C@@H](CC3=CC=C(Cl)C=C3Cl)CN
In vitro antitumor activity: Scientists from Curis, Inc tested the growth inhibitory effects of CUDC-305 against a total of 40 human cancer cell lines, including 34 solid and 6 hematologic tumorÂ–derived lines. CUDC-305 inhibited the proliferation of these cancer cell lines with an IC50, ranging from 40 to 900 nmol/L (mean IC50, 220 nmol/L). CUDC-305 shows high affinity for HSP90alpha/beta (IC(50), approximately 100 nmol/L) and HSP90 complex derived from cancer cells (IC(50), 48.8 nmol/L). CUDC-305 exhibits high oral bioavailability (96.0%) and selective retention in tumor (half-life, 20.4 hours) compared with normal tissues. Furthermore, CUDC-305 can cross blood-brain barrier and reach therapeutic levels in brain tissue. CUDC-305 exhibits dose-dependent antitumor activity in an s.c. xenograft model of U87MG glioblastoma and significantly prolongs animal survival in U87MG orthotopic model. CUDC-305 also displays potent antitumor activity in animal models of erlotinib-resistant non-small cell lung cancer and induces tumor regression in animal models of MDA-MB-468 breast cancer and MV4-11 acute myelogenous leukemia. Correlating with its efficacy in these various tumor models, CUDC-305 robustly inhibits multiple signaling pathways, including PI3K/AKT and RAF/MEK/ERK, and induces apoptosis. In combination studies, CUDC-305 enhances the antitumor activity of standard-of-care agents in breast and colorectal tumor models. CONCLUSION: CUDC-305 is a promising drug candidate for the treatment of a variety of cancers, including brain malignancies. (source: Clin Cancer Res. 2009 Jun 15;15(12):4046-57.).
1: Bao R, Lai CJ, Wang DG, Qu H, Yin L, Zifcak B, Tao X, Wang J, Atoyan R, Samson M, Forrester J, Xu GX, DellaRocca S, Borek M, Zhai HX, Cai X, Qian C. Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer. Mol Cancer Ther. 2009 Dec;8(12):3296-306. Epub . PubMed PMID: 19952121.