| Identification | Back Directory | [Name]
1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- | [CAS]
1863952-15-1 | [Synonyms]
CB-5339
1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide
1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- | [Molecular Formula]
C24H24N6O | [MOL File]
1863952-15-1.mol | [Molecular Weight]
412.49 |
| Chemical Properties | Back Directory | [Boiling point ]
751.8±70.0 °C(Predicted) | [density ]
1.38±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 41.67 mg/mL | [form ]
Solid | [pka]
16.12±0.30(Predicted) | [color ]
Off-white to yellow | [InChIKey]
XDHFSLWWYBVSLN-UHFFFAOYSA-N | [SMILES]
N1(C2=NC(NCC3=CC=CC=C3)=C3CCCNC3=N2)C2=C(C(C(N)=O)=CC=C2)C=C1C |
| Hazard Information | Back Directory | [Uses]
CB-5339 is an oral activity potent p97 inhibitor with an IC50 <30 nM. CB-5339 can be used for leukemia research[1]. CB-5339 extracted from WO2015109285A1 compound FF07. | [Biological Activity]
CB-5339 is a second generation, potent and selective, orally bioavailable, ATP-competitive, small molecule inhibitor of valosin containing protein (VCP)/p97 [1,2]. CB-5339 is an ATP-competitive, small molecule inhibitor of p97 with IC50 of 53 nM [3].
CB-5339 effectively effect on a panel of 16 primary AML patient samples harboring diverse genetic backgrounds. The median IC50 value was 375 nM among these samples [1]. CB-5339 (200 to 1000 nM for 48 hours) induces in vitro loss of viability in AML cell lines (OCI-AML3, MOLM13, SET2 and HEL92.1.7 cells), as well as in fresh, patient-derived (PD) AML cells, including those with TP53 mutations and/or TP53 allelic loss, or with 3q26 (MECOM locus) lesions and EVI1 overexpression [2]. CB-5339 induced accumulation of polyubiquitylated proteins, retention of ERAD substrates, and lethal ER stress in cancer cells mediated by CHOP, DR5 and NOXA [2].
CB-5339 has higher bioavailability than CB-5083 [1]. Treatment with CB-5339 (90 mg/kg) reduced invasion of myeloid leukemia and prolonged survival in an MLL-AF9-driven PDX AML mouse model [1]. In a tail-vein infused, luciferase transduced, aggressive xenograft model of MOLM13 cells, after AML engraftment, co-treatment for 3 weeks with CB-5339 (50 mg/kg/day, PO) and either venetoclax (30 mg/kg/day, PO) or OTX015 (30 mg/kg/day, PO), as compared to treatment with vehicle or each drug alone, significantly reduced the AML burden and improved median and overall survival of the NSG mice, without inducing significant toxicity [2]. | [in vivo]
CB-5339 (90 mg/kg for p.o.) decreases bone marrow leukemic infiltration and prolongs mice survival in MLL-AF9-driven patient-derived xenograft (PDX) AML mouse model[2].
| Animal Model: | MLL-AF9-driven patient-derived xenograft (PDX) AML model in C57BL/6 male mice[2] | | Dosage: | 90 mg/kg | | Administration: | oral gavage (p.o.) | | Result: | Decreased bone marrow leukemic infiltration and circulating leukemic cells.
Prolonged mice survival.
|
| [storage]
Store at -20°C | [References]
[1]. B Roux B, Vaganay C, Vargas J D, et al. Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor[J]. Science translational medicine, 2021, 13(587): eabg1168.[2]. Fiskus W C, Das K, Mill C P, et al. Efficacy of Vcp/p97 Inhibitor, CB-5339, Alone and in Combinations Against High-Risk AML, Including Those with Genetic Lesion in TP53[J]. Blood, 2022, 140(Supplement 1): 8807-8808.[3]. Wang X, Wen T, Miao H, et al. Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of colorectal cancer[J]. Bioorganic & Medicinal Chemistry, 2022, 74: 117050. |
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| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
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