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.

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	X-376	X-376 is a highly selective and potent inhibitor of ALK (anaplastic lymphoma kinase) tyrosine kinase, demonstrating strong activity with an IC50 of 0.61 nM. While it primarily targets ALK, it also exhibits inhibitory effects on MET kinase, though with slightly reduced potency (IC50 = 0.69 nM). Due to its robust kinase-blocking properties, X-376 shows significant anti-tumor efficacy, making it a promising candidate for cancer research and therapeutic development.
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.