BIX 01294 Trihydrochloride|CAS 1392399-03-9

Cas No.:	1392399-03-9
Chemical Name:	BIX01294 HCl
Synonyms:	BIX 01294;BIX 01294 Trihydrochloride Hydrate;Trihydrochloride Hydrate;BIX 01294 Trihydrochloride;4-Quinazolinamine, 2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-, hydrochloride (1:3);N-(1-Benzyl-4-piperidinyl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan -1-yl)-4-quinazolinamine trihydrochloride;2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine Trihydrochloride Hydrate;2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrochloride (1:3)
SMILES:	Cl.Cl.Cl.CN1CCCN(C2N=C(NC3CCN(CC4C=CC=CC=4)CC3)C3=CC(=C(C=C3N=2)OC)OC)CC1
Formula:	C₂₈H₄₁Cl₃N₆O₂
M.Wt:	600.026
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	BIX-01294 trihydrochloride is a reversible and highly selective G9a Histone Methyltransferase inhibitor, with an IC50 of 2.7 μM in DELFIA assay. BIX-01294 trihydrochloride specifically inhibits G9a (H3K9me2) and GLP enzyme (H3K9me3), with IC50s of 1.7 μM and 38 μM, respectively. BIX-01294 trihydrochloride inhibits G9a/GLP by competing for binding with the amino acids N-terminal of the substrate lysine residue. BIX-01294 trihydrochloride, a (1H-1,4-diazepin-1-yl)-quinazolin-4-yl amine derivative, induces necroptosis and autophagy. BIX-01294 trihydrochloride has antitumor activity in recurrent tumor cells[1][2][3][4].
Target:	IC50: 2.7 μM (G9a in DELFIA assay)[2] IC50: 1.7 μM for G9a (H3K9me2) and 38 μM for GLP (H3K9me3)[2]
In Vivo:	BIX-01294 trihydrochloride (10 mg/kg; IP; three times a week for 2 weeks) significantly reduces tumor growth and tumor burden in recurrent tumor cells. Primary tumor growth is not inhibited[1]. Animal Model: Female MMTV-rtTA;TetO-Her2/neu (MTB;TAN) and TetO-Her2/neu (TAN) mice with recurrent or primary tumor cells[1] Dosage: 10 mg/kg Administration: IP; three times a week for 2 weeks Result: Significantly reduced tumor growth and tumor burden in recurrent tumor cells. Primary tumor growth was not inhibited. Slowed the growth of orthotopic recurrent tumors in athymic nude recipients.
In Vitro:	BIX-01294 (2 μM; 48 h) trihydrochloride selectively inhibits recurrent tumor cell growth[1]. BIX-01294 (1 μM) trihydrochloride leads to a marked increase in phosphorylation of S345 of MLKL[1]. BIX-01294 (1 μM) trihydrochloride significantly upregulates the canonical p53 targets Cdkn1a (p21) and Gadd45a in recurrent tumor cell lines[1]. BIX-01294 (1 μM; 6 days) trihydrochloride causes the reduction in H3K9me2 levels in primary and recurrent tumor cells[1]. BIX-01294 trihydrochloride leads to necroptotic cell death in recurrent tumor cells. Necrostatin-1 (30 μM) partially reverses cell death induced by BIX-01294 (750 nM; 24 h) trihydrochloride[1]. BIX-01294 (4.1 μM; for 2 days) trihydrochloride causes around a 20% reduction, concomitant with a comparable increase in the unmodified H3K9 fragment in H3K9me2 in mouse ES cells. BIX-01294 trihydrochloride causes pronounced reduction in H3K9me2 and a small decrease for H3K9me3 and H3K9me1 in wild-type ES cells[2]. BIX-01294 trihydrochloride has no inhibition of the other histone methyltransferases even at concentrations of 45 μM. BIX-01294 trihydrochloride does not affect SUV39H1 (H320R) and PRMT1 within the tested concentration range (up to 10 μM)[2]. BIX-01294 trihydrochloride inhibits G9a in an uncompetitive manner with S-adenosyl-methionine (SAM)[2]. BIX-01294 (1 µg/mL) causes reduction in the BrdU incorporation of fetal PASMCs. BIX-01294 treatment decreases the PASMCs migration induced by PDGF[3]. Cell Viability Assay[1] Cell Line: Primary or recurrent tumor cells Concentration: 2 μM Incubation Time: 48 h Result: Selectively inhibited recurrent tumor cell growth.
References:	[1]. Nathaniel W Mabe, et al. G9a Promotes Breast Cancer Recurrence through Repression of a Pro-inflammatory Program. Cell Rep. 2020 Nov 3;33(5):108341. [2]. Stefan Kubicek, et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007 Feb 9;25(3):473-81. [3]. Yang Q, et al. BIX-01294 treatment blocks cell proliferation, migration and contractility in ovine foetal pulmonary arterial smooth muscle cells. Cell Prolif. 2012 Aug;45(4):335-44. [4]. Iwona Anna Ciechomska, et al. BIX01294, an inhibitor of histone methyltransferase, induces autophagy-dependent differentiation of glioma stem-like cells. Sci Rep

Cat. No.	Product name	Field of application
DC60859	MT-125(MT 125)	MT125 is a brain-penetrant small-molecule inhibitor selectively targeting non-muscle myosin IIA/B (NMIIA/B) with >20-fold specificity over cardiac myosin. It demonstrates potent anti-glioblastoma activity by: (1) blocking tumor invasion and cytokinesis (inducing polyploidy), (2) disrupting mitochondrial dynamics to elevate ROS and trigger ferroptosis, and (3) sensitizing tumors to radiotherapy/kinase inhibitors via ROS-driven PDGFR/mTOR pathway activation. Subcutaneous administration achieves brain concentrations twice plasma levels (t_1/2~10.5 hr) with no toxicity observed at 15× the therapeutic dose in rats. MT-125 monotherapy extends survival in GBM models, while combinations with PDGFR/PI3K inhibitors induce long-term remission (>40% mice). Its first-in-class mechanism, safety profile, and CNS bioavailability support clinical development for glioblastoma.
DC60781	TRPC6 activator compound 2	TRPC6 activator compound 2 is selective activator of TRPC6 that does not potentiate TRPC3 and mTRPC7. Comp2 is able to cross BBB.
DC66546	R-Sirpiglenastat	R-Sirpiglenastat is the R- isomer of Sirpiglenastat(DRP-104).Sirpiglenastat (DRP104) is a broad acting glutamine antagonist. Sirpiglenastat has anticancer effects by directly targeting tumor metabolism and simultaneously inducing a potent antitumor immune response.
DC60597	AZD0780	AZD0780 is the first oral small molecule PCSK9 inhibitor for the treatment of hypercholesterolemia.
DC90056	PLX-5622 HCl form (water solubility form)	PLX5622 is the HCl salt form of PLX-5622, which has better water solubility.PLX-5622 is a highly selective brain-penetrant CSF1R inhibitor (IC50=0.016 µM; Ki=5.9 nM) allowing for extended and specific microglial elimination, preceding and during pathology development.
DC65830	1-M-PES(1-Methoxy-5-methylphenazinium ethyl sulfate)	1-m-PES is an electron mediator which has higher stability of solutions than 1-Methoxy PMS. The stability in neutral to alkali conditions has been extremely improved with 1-Methoxy PES. 1-M-PES is a stable small-molecular compound and it has an equal or higher thermal stability than diaphorase. The 1-Methoxy PES solution can be stored long term.
DC65821	Upadacitinib hemihydrate	Upadacitinib (ABT-494) is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM, being developed for the treatment of several autoimmune disorders.
DC65697	HDAC6 inhibitor 4510	A novel and seletive HDAC6 inhibitor.
DC65676	Fenretinide Glucuronide Monosodium Salt	Fenretinide Glucuronide Monosodium Salt, is the metabolite of Fenretinide (F250000), which is a synthetic retinoid deriverative, substances related to vitamin A. They are also shown to be used for the treatment of cancer, as well as in the treatment of cystic fibrosis, rheumatoid arthritis, acne, and psoriasis.
DC89083	Pacritinib citrate	Pacritinib Citrate is the citrate salt form of pacritinib, an orally bioavailable inhibitor of Janus kinase 2 (JAK2).