WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 408066
CAS#: 2355377-13-6 (free acid)
Description: DDO-5936 is a potent PPI inhibitor targeting Hsp90-Cdc37 protein-protein interaction (PPI) as Orally Active Inhibitors for the Treatment of Colorectal Cancer. DDO-5936 disrupted the Hsp90-Cdc37 PPI both in vitro and in vivo via binding to a previously unknown site on Hsp90 involving Glu47, one of the binding determinants for the Hsp90-Cdc37 PPI, leading to selective down-regulation of Hsp90 kinase clients in HCT116 cells. In addition, inhibition of Hsp90-Cdc37 complex formation by DDO-5936 resulted in a remarkable cyclin-dependent kinase 4 decrease and consequent inhibition of cell proliferation through Cdc37-dependent cell cycle arrest.
MedKoo Cat#: 408066
Name: DDO-5936
CAS#: 2355377-13-6 (free acid)
Chemical Formula: C25H29N5O4S
Exact Mass: 495.194
Molecular Weight: 495.598
Elemental Analysis: C, 60.59; H, 5.90; N, 14.13; O, 12.91; S, 6.47
Related CAS #: 2355377-13-6 (free acid) DDO5936 sodium
Synonym: DDO-5936; DDO 5936; DDO5936;
IUPAC/Chemical Name: N-(Mesitylsulfonyl)-N-(4-((2-(pyrrolidin-1-yl)pyrimidin-4-yl)amino)phenyl)glycine
InChi Key: IIPYRKNROAWEPK-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H29N5O4S/c1-17-14-18(2)24(19(3)15-17)35(33,34)30(16-23(31)32)21-8-6-20(7-9-21)27-22-10-11-26-25(28-22)29-12-4-5-13-29/h6-11,14-15H,4-5,12-13,16H2,1-3H3,(H,31,32)(H,26,27,28)
SMILES Code: O=C(O)CN(S(=O)(C1=C(C)C=C(C)C=C1C)=O)C2=CC=C(NC3=NC(N4CCCC4)=NC=C3)C=C2
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Hsp90-Cdc37 protein-protein interaction. |
| In vitro activity: | Based on a first specific small-molecule inhibitor targeting Hsp90-Cdc37 PPI (DDO-5936), which was previously reported by this group, a preliminary investigation of the structure-activity relationships and pharmacodynamic evaluations was conducted to improve the potency and drug-like properties. Here, efforts resulted in the currently best inhibitor 18h with improved binding affinity (Kd = 0.5 μM) and cellular inhibitory activity (IC50 = 1.73 μM). Both in vitro and in vivo assays revealed that 18h could efficiently block the Hsp90-Cdc37 interaction to specifically inhibit kinase clients of Hsp90. Furthermore, 18h showed ideal physiochemical properties with favorable stability, leading to an oral efficacy in vivo. Reference: Wang L, Jiang J, Zhang L, Zhang Q, Zhou J, Li L, Xu X, You Q. Discovery and Optimization of Small Molecules Targeting the Protein-Protein Interaction of Heat Shock Protein 90 (Hsp90) and Cell Division Cycle 37 as Orally Active Inhibitors for the Treatment of Colorectal Cancer. J Med Chem. 2020 Feb 13;63(3):1281-1297. doi: 10.1021/acs.jmedchem.9b01659. Epub 2020 Jan 24. PMID: 31935086. |
| In vivo activity: | Here, DDO-5936 as a small-molecule inhibitor of the Hsp90-Cdc37 protein-protein interaction (PPI) was indenitified in colorectal cancer. DDO-5936 disrupted the Hsp90-Cdc37 PPI both in vitro and in vivo via binding to a previously unknown site on Hsp90 involving Glu47, one of the binding determinants for the Hsp90-Cdc37 PPI, leading to selective down-regulation of Hsp90 kinase clients in HCT116 cells. In addition, inhibition of Hsp90-Cdc37 complex formation by DDO-5936 resulted in a remarkable cyclin-dependent kinase 4 decrease and consequent inhibition of cell proliferation through Cdc37-dependent cell cycle arrest. Together, results demonstrated DDO-5936 as an identified specific small-molecule inhibitor of the Hsp90-Cdc37 PPI that could be used to comprehensively investigate alternative approaches targeting Hsp90 chaperone cycles for cancer therapy. Reference: Wang L, Zhang L, Li L, Jiang J, Zheng Z, Shang J, Wang C, Chen W, Bao Q, Xu X, Jiang Z, Zhang J, You Q. Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer. Sci Adv. 2019 Sep 18;5(9):eaax2277. doi: 10.1126/sciadv.aax2277. PMID: 31555737; PMCID: PMC6750927. |
The following data is based on the product molecular weight 495.598 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | Wang L, Jiang J, Zhang L, Zhang Q, Zhou J, Li L, Xu X, You Q. Discovery and Optimization of Small Molecules Targeting the Protein-Protein Interaction of Heat Shock Protein 90 (Hsp90) and Cell Division Cycle 37 as Orally Active Inhibitors for the Treatment of Colorectal Cancer. J Med Chem. 2020 Feb 13;63(3):1281-1297. doi: 10.1021/acs.jmedchem.9b01659. Epub 2020 Jan 24. PMID: 31935086. |
| In vitro protocol: | Wang L, Jiang J, Zhang L, Zhang Q, Zhou J, Li L, Xu X, You Q. Discovery and Optimization of Small Molecules Targeting the Protein-Protein Interaction of Heat Shock Protein 90 (Hsp90) and Cell Division Cycle 37 as Orally Active Inhibitors for the Treatment of Colorectal Cancer. J Med Chem. 2020 Feb 13;63(3):1281-1297. doi: 10.1021/acs.jmedchem.9b01659. Epub 2020 Jan 24. PMID: 31935086. |
| In vivo protocol: | Wang L, Zhang L, Li L, Jiang J, Zheng Z, Shang J, Wang C, Chen W, Bao Q, Xu X, Jiang Z, Zhang J, You Q. Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer. Sci Adv. 2019 Sep 18;5(9):eaax2277. doi: 10.1126/sciadv.aax2277. PMID: 31555737; PMCID: PMC6750927. |
1: Wang L, Jiang J, Zhang L, Zhang Q, Zhou J, Li L, Xu X, You Q. Discovery and Optimization of Small Molecules Targeting the Protein-Protein Interaction of Heat Shock Protein 90 (Hsp90) and Cell Division Cycle 37 as Orally Active Inhibitors for the Treatment of Colorectal Cancer. J Med Chem. 2020 Feb 13;63(3):1281-1297. doi: 10.1021/acs.jmedchem.9b01659. Epub 2020 Jan 24. PMID: 31935086.
2: Wang L, Zhang L, Li L, Jiang J, Zheng Z, Shang J, Wang C, Chen W, Bao Q, Xu X, Jiang Z, Zhang J, You Q. Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer. Sci Adv. 2019 Sep 18;5(9):eaax2277. doi: 10.1126/sciadv.aax2277. PMID: 31555737; PMCID: PMC6750927.
Cell division cycle 37 (Cdc37) is known to work as a kinase-specific cochaperone, which selectively regulates the maturation of kinases through protein-protein interaction (PPI) with Hsp90. Directly disrupting the Hsp90-Cdc37 PPI is emerging as an alternative strategy to develop anticancer agents through a specific inhibition manner of kinase clients of Hsp90
