1095382-05-0

Basic information

• Product Name: CCT 137690
• Synonyms: CCT 137690;6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridine;3-[[4-[6-Bromo-2-[4-(4-methylpiperazin-1-yl)phenyl]-3H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-5-methylisoxazole CCT-137690;CCT137690, >=98%;3-((4-(6-Bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-
• CAS NO: 1095382-05-0
• Molecular Formula: C₂₆H₃₁BrN₈O
• Molecular Weight: 551.5
• Product Categories: Inhibitor;Inhibitors
• Mol File: 1095382-05-0.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Density: 1.424
• Solubility: insoluble in H2O; insoluble in EtOH; ≥6.89 mg/mL in DMSO
• CAS DataBase Reference: CCT 137690(CAS DataBase Reference)
• NIST Chemistry Reference: CCT 137690(1095382-05-0)
• EPA Substance Registry System: CCT 137690(1095382-05-0)

Safety Data

• Hazardous Substances Data: 1095382-05-0(Hazardous Substances Data)

Usage

Uses

CCT 137690 is used in the treatment of acute myeloid leukemia.

Biological Activity

cct137690 is an orally bioavailable inhibitor of aurora kinases with ic50 values in a range from 15 to 25 nm [1].aurora kinase is a family of serine/threonine kinases including aurora-a, b and c. they play important roles in the regulation of mitosis and take participate in the causation and progression of various tumors including ovarian, breast, glioma and colon. therefore aurora kinases have been regarded as anti-cancer targets in cancer chemotherapeutics.cct137690 is a selective small-molecular inhibitor of aurora kinases and showed anti-tumor activities both in vitro and in vivo. besides that, cct137690 exerted good stability in mouse liver microsomes [1].when tested toward a panel of 94 kinases, cct137690inhibited 80% activities of veg-fr, aurora-a, and fgf-r1 at concentration of 1 μm. it suppressed the phosphorylation of histone h3 caused by aurora-b. the ic50 values of cct137690 against aurora-b and c were 25 and 19 nm, respectively. cct137690 showed potent anti-proliferation effects on various kinds of tumors such as a2780 ovarian tumor cell (ic50 value of 140 nm), sw620 (ic50 value of 300 nm) and sw48 colon carcinoma (ic50 value of 157 nm). it caused cell cycle perturbations. in addition, cct137690 was found to have synergistic effects with radiotherapy. it increased the sensitivity of sw620 cells to radiation. the combination treatment resulted in much more cell death through apoptosis [1 and 2].in mice model bearing sw620 xenografts, administration of cct137690slowed the growth of tumors without observed toxicity. the ratio of treat/control group based on tumor weight was 37% at the dose of 75 mg/kg. besides that, cct137690 was found to significantly reduced neuroblastoma tumor mass in mycn transgenic mice, which meant cct137690 could benefit patients with mycn-amplified neuroblastoma [1 and 3].

references

[1] bavetsias v, large j m, sun c, et al. imidazo [4, 5-b] pyridine derivatives as inhibitors of aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. journal of medicinal chemistry, 2010, 53(14): 5213-5228.[2] wu x, liu w, cao q, et al. inhibition of aurora b by cct137690 sensitizes colorectal cells to radiotherapy. j expclin cancer res, 2014, 33(1): 13.[3] faisal a, vaughan l, bavetsias v, et al. the aurora kinase inhibitor cct137690 downregulates mycn and sensitizes mycn-amplified neuroblastoma in vivo. molecular cancer therapeutics, 2011, 10(11): 2115-2123.

Upstream product

• 942949-26-0 5-bromo-4-[4-[(5-methyl-isoxazol-3-yl)methyl]piperazin-1-yl]-3-nitro-pyridin-2-ylamine 
• 27913-99-1 4-(4-methylpiperazin-1-yl) benzaldehyde 

Relevant articles and documents

Imidazo[4,5-b]pyridine derivatives as inhibitors of aurora kinases: Lead optimization studies toward the identification of an orally bioavailable preclinical development candidate

Lead optimization studies using 7 as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors of Aurora kinases that possessed the 1-benzylpiperazinyl motif at the 7-position, and displayed favorable in vitro properties. Cocrystallization of Aurora-A with 40c (CCT137444) provided a clear understanding into the interactions of this novel class of inhibitors with the Aurora kinases. Subsequent physicochemical property refinement by the incorporation of solubilizing groups led to the identification of 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b] pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole (51, CCT137690) which is a potent inhibitor of Aurora kinases (Aurora-A IC50 = 0.015 ± 0.003 μM, Aurora-B IC50 = 0.025 μM, Aurora-C IC50 = 0.019 μM). Compound 51 is highly orally bioavailable, and in in vivo efficacy studies it inhibited the growth of SW620 colon carcinoma xenografts following oral administration with no observed toxicities as defined by body weight loss.