KRCA-0008|cas 1472795-20-2|DC Chemicals

Cas No.:	1472795-20-2
Chemical Name:	1,1'-(4,4'-(((5-Chloropyrimidine-2,4-diyl)bis(azanediyl))bis(3-methoxy-4,1-phenylene))bis(piperazine-4,1-diyl))diethanone
Synonyms:	KRCA 0008;KRCA-008;1,1′-[(5-Chloro-2,4-pyrimidinediyl)bis[imino(3-methoxy-4,1-phenylene)-4,1-piperazinediyl]]bis-ethanone;KRCA-0008;1,1'-(4,4'-(((5-Chloropyrimidine-2,4-diyl)bis(azanediyl))bis(3-methoxy-4,1-phenylene))bis(piperazine-4,1-diyl))diethanone;1,1'-[(5-Chloro-2,4-pyrimidinediyl)bis[imino(3-methoxy-4,1-phenylene)-4,1-piperazinediyl]]bisethanone;1-[4-[4-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]-3-methoxyphenyl]piperazin-1-yl]ethanone;C30H37ClN8O4;KRCA0008;AOB2894;BDBM193425;BCP16229;3767AH
SMILES:	ClC1=C([H])N=C(N=C1N([H])C1C([H])=C([H])C(=C([H])C=1OC([H])([H])[H])N1C([H])([H])C([H])([H])N(C(C([H])([H])[H])=O)C([H])([H])C1([H])[H])N([H])C1C([H])=C([H])C(=C([H])C=1OC([H])([H])[H])N1C([H])([H])C([H])([H])N(C(C([H])([H])[H])=O)C([H])([H])C1([H])[H]
Formula:	C₃₀N₈O₄ClH₃₇
M.Wt:	609.119
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:

KRCA-0008 is a potent and selective ALK/Ack1 inhibitor with IC50 of 12 nM/4 nM for ALK and Ack1 respectively; displays drug-like properties without hERG liability.IC50 value: 12 nM/4 nM(ALK/Ack1) [1]Target: ALK/Ack1 inhibitorKRCA-0008 retains good drug-like properties: good water-solubility (54 μM in 5% DMSO–water, 150 μM in 5% DMSO–PBS buffer) with moderate plasma protein binding (93% in rat) and low brain exposure (Cbrain/Cplasma = ～0.02). It has good liver microsomal stability (% remaining after 30 min: 52% in mouse, 89% in rat, 72% in human) and little to no CYP inhibition (1A2, 2C9, 2D6, 3A4 @ 10 μM). It does not appear to cause hERG blockade (patch clamp IC50 = 30 μM) and is negative on Ames test (1000 μg/plate), chromosomal aberration assay and micronucleus assay.KRCA-0008 also shows promising pharmacokinetic parameters in both mice and rat (oral bioavailability = 66–94.5%). KRCA-0008 shows a modest tumor growth inhibition in vivo activity in H3122 human lung cancer bearing mice model comparable to Crizotinib without significant body weight change. It is important to mention the KRCA-0008 25 mpk and 50 mpk groups did not show dose-dependent tumor growth inhibition.

References:

[1]. Park CH, et al. Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment. Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6.

MSDS

COA

LOT NO.	DOWNLOAD

2018-0101
2018-0101

Cat. No.	Product name	Field of application
DC10463	Repotrectinib(TPX-005)	Repotrectinib(TPX-005) is a multi-target macrocycle inhibitor of anaplastic lymphoma kinase (ALK), c-ros proto-oncogene 1 receptor tyrosine kinase (ROS1), and neurotrophic tyrosine kinase receptor (TRK)
DC2047	Crizotinib (PF-2341066)	PF-2341066 (Crizotinib) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nnM, respectivley.
DC7924	PF06463922(Lorlatinib)	PF06463922 is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity.
DC7303	NVP-TAE684	NVP-TAE684(TAE684) is a highly potent and selective small-molecule ALK inhibitor, which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM.
DC8034	LDN193189 free base	LDN193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively.
DC8127	KRCA-0008	KRCA-0008 is a potent Ack1 and anaplastic lymphoma kinase (ALK) dual inhibitor (IC50 values are 4 and 12 nM respectively).
DC10547	Ensartinib	Ensartinib is a potent inhibitor of ALK, which is used to treat non-small-cell lung cancer.
DC8728	CH5424802(Alectinib HCl)	CH5424802(AF 802; Alectinib) is a potent ALK inhibitor with IC50 of 1.9 nM, sensitive to L1196M mutation.
DC8138	CEP-28122	CEP-28122 is a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancers.
DC7359	Asp-3026	ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM.