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MedKoo Cat#: 407950 | Name: CCT241736
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

CCT241736 is a potent and orally active and dual FLT3-Aurora inhibitor. CCT241736 has IC50 values against FLT3, Aurora A and Aurora B of 0.035, 0.015 and 0.1 μM respectively. CCT241736 inhibits a wide range of FLT3 mutants, including FLT3-ITD, -D835Y, -D835H, -K663Q and -N841I. In cellular assays, CCT241736 inhibits viability of the human FLT3-ITD positive AML cell lines MOLM-13 and MV-4;11 with EC50 values of 0.1 and 0.27

Chemical Structure

CCT241736
CCT241736
CAS#1402709-93-6

Theoretical Analysis

MedKoo Cat#: 407950

Name: CCT241736

CAS#: 1402709-93-6

Chemical Formula: C22H23Cl2N7

Exact Mass: 455.1392

Molecular Weight: 456.38

Elemental Analysis: C, 57.90; H, 5.08; Cl, 15.54; N, 21.48

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,450.00 2 Weeks
1g USD 3,950.00 2 Weeks
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Related CAS #
No Data
Synonym
CCT241736; CCT-241736; CCT 241736; mobinitinibum; mobinitinib
IUPAC/Chemical Name
6-chloro-7-[4-[(4-chlorophenyl)methyl]-1-piperazinyl]-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine
InChi Key
AKJBLKUZXRMECW-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H23Cl2N7/c1-14-17(13-29(2)28-14)21-26-19-20(18(24)11-25-22(19)27-21)31-9-7-30(8-10-31)12-15-3-5-16(23)6-4-15/h3-6,11,13H,7-10,12H2,1-2H3,(H,25,26,27)
SMILES Code
CC1=NN(C)C=C1C2=NC3=C(N4CCN(CC5=CC=C(Cl)C=C5)CC4)C(Cl)=CN=C3N2
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
2934.99.03.00
More Info
M respectively. In vivo, mouse tumor xenograft models of MOLM-13, MV-4;11 and the doubly-mutated cell line, MOLM-13-RES, are also sensitive to CCT241736, with biomarker modulation consistent with dual inhibition of FLT3 and Aurora kinases. In summary, dual inhibition of FLT3 and the critical mitotic kinase Aurora by CCT241736 may represent a novel treatment strategy for FLT3-mutated AML by overcoming the effects of high FL levels and limiting resistance caused by secondary mutations of the FLT3 gene.
Product Data
Product Data
Instruction
View handling instruction
Biological target:
CCT241736 is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor, which inhibits Aurora kinases (Aurora-A Kd, 7.5 nM, IC50, 38 nM; Aurora-B Kd, 48 nM), FLT3 kinase (Kd, 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd, 38 nM) and FLT3(D835Y) (Kd, 14 nM).
In vitro activity:
CCT241736 (Compound 27e) is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor, which inhibits Aurora kinases (Aurora-A Kd, 7.5 nM, IC50, 38 nM, Aurora-B Kd, 48 nM), FLT3 kinase (Kd, 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd, 38 nM) and FLT3(D835Y) (Kd, 14 nM). CCT241736 exhibits antiproliferative activity in a range of human tumor cell lines, such as HCT116 human colon carcinoma (GI50, 0.300 μM), the human FLT3-ITD positive AML cell lines MOLM-13 (GI50, 0.104 μM) and MV4-11 (GI50, 0.291 μM). CCT241736 also inhibits both the autophosphorylation of Aurora-A at T288 (a biomarker for Aurora-A inhibition: IC50, 0.030 μM) and histone H3 phosphorylation at S10 (a biomarker for Aurora-B inhibition: IC50, 0.148 μM), consistent with potent cellular activity versus both Aurora-A and -B. CCT241736 suppresses Aurora-A in MOLM-13 cells with concomitant inhibition of FLT3 signaling. Reference: J Med Chem. 2012 Oct 25;55(20):8721-34. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23043539/
In vivo activity:
Human tumor xenograft experiments (MOLM-13) were carried out in athymic mice to evaluate the efficacy of CCT241736 in vivo. CCT241736 reduced tumor growth compared with that in vehicle-treated mice in a dose-dependent manner with no observed toxicity on chronic dosing (Figure 3A). To analyze the PD activity of CCT241736 in vivo, tumors were collected at 2 hours after the final dose, and the lysates were analyzed by immunoblotting. Reduction of phospho-Aurora-A and phospho-STAT5 indicates inhibition of both Aurora A and FLT3 in a dose-dependent manner (Figure 3B). Similarly, survivin levels were reduced in a dose-dependent manner, which indicates that CCT241736 induced apoptosis in vivo. A confirmatory study in a second in vivo FLT3-ITD+ AML human tumor xenograft model (MV4-11) showed that CCT241736 significantly inhibits the growth of MV4-11 xenografts with clear inhibition of both HH3 and STAT5 phosphorylation at 2 hours after the final dose, indicating a dual inhibition of both Aurora and FLT3 downstream pathways in the tumor.15 To demonstrate that Aurora kinase inhibition by CCT241736 makes a significant contribution to efficacy in FLT3-mutated AML, samples of the MV4-11 tumors from the animals dosed with 100 mg/kg at 2 hours after administration were analyzed by immunofluorescence microscopy. More than one third (36%) of mitotic cells from tumors treated with CCT241736 formed monopolar or abnormal spindles, a typical phenotype for Aurora kinase inhibition.23 In comparison, this phenotype was observed in only 4% of mitotic cells in tumors from mice treated with vehicle control (Figure 3C-D). These data confirm the contribution of Aurora inhibition by CCT241736 to the in vivo efficacy and the already known induced phenotype from previous studies using Aurora inhibitors. Reference: Blood Adv. 2020 Apr 14;4(7):1478-1491. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32282883/
Solvent mg/mL mM
Solubility
DMSO 75.0 164.34
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 456.38 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.

Recalculate based on batch purity %
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:
In vitro protocol:
1. Bavetsias V, Crumpler S, Sun C, Avery S, Atrash B, Faisal A, Moore AS, Kosmopoulou M, Brown N, Sheldrake PW, Bush K, Henley A, Box G, Valenti M, de Haven Brandon A, Raynaud FI, Workman P, Eccles SA, Bayliss R, Linardopoulos S, Blagg J. Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia. J Med Chem. 2012 Oct 25;55(20):8721-34. doi: 10.1021/jm300952s. Epub 2012 Oct 8. PMID: 23043539; PMCID: PMC3483018. 2. Wood FL, Shepherd S, Hayes A, Liu M, Grira K, Mok Y, Atrash B, Faisal A, Bavetsias V, Linardopoulos S, Blagg J, Raynaud FI. Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species. Eur J Pharm Sci. 2019 Nov 1;139:104899. doi: 10.1016/j.ejps.2019.04.004. Epub 2019 Apr 3. PMID: 30953752; PMCID: PMC6892276.
In vivo protocol:
1. Bavetsias V, Crumpler S, Sun C, Avery S, Atrash B, Faisal A, Moore AS, Kosmopoulou M, Brown N, Sheldrake PW, Bush K, Henley A, Box G, Valenti M, de Haven Brandon A, Raynaud FI, Workman P, Eccles SA, Bayliss R, Linardopoulos S, Blagg J. Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia. J Med Chem. 2012 Oct 25;55(20):8721-34. doi: 10.1021/jm300952s. Epub 2012 Oct 8. PMID: 23043539; PMCID: PMC3483018. 2. Moore AS, Faisal A, Mak GWY, Miraki-Moud F, Bavetsias V, Valenti M, Box G, Hallsworth A, de Haven Brandon A, Xavier CPR, Stronge R, Pearson ADJ, Blagg J, Raynaud FI, Chopra R, Eccles SA, Taussig DC, Linardopoulos S. Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736. Blood Adv. 2020 Apr 14;4(7):1478-1491. doi: 10.1182/bloodadvances.2019000986. PMID: 32282883; PMCID: PMC7160287.
1: Moore AS, Faisal A, Mak GWY, Miraki-Moud F, Bavetsias V, Valenti M, Box G, Hallsworth A, de Haven Brandon A, Xavier CPR, Stronge R, Pearson ADJ, Blagg J, Raynaud FI, Chopra R, Eccles SA, Taussig DC, Linardopoulos S. Quizartinib- resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736. Blood Adv. 2020 Apr 14;4(7):1478-1491. doi: 10.1182/bloodadvances.2019000986. PMID: 32282883; PMCID: PMC7160287. 2: Wood FL, Shepherd S, Hayes A, Liu M, Grira K, Mok Y, Atrash B, Faisal A, Bavetsias V, Linardopoulos S, Blagg J, Raynaud FI. Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species. Eur J Pharm Sci. 2019 Nov 1;139:104899. doi: 10.1016/j.ejps.2019.04.004. Epub 2019 Apr 3. PMID: 30953752; PMCID: PMC6892276.