Varlitinib (ARRY334543) is a potent, selective ErbB1(EGFR) and ErbB2(HER2) inhibitor with IC50 of 7 nM and 2 nM, respectively. Phase 2.

 

Brand: BCM

 

Target: HER

 

Signaling Pathways: Angiogenesis; JAK/STAT signaling; Tyrosine Kinase/Adaptors

 

In Vitro: ARRY334543 is a reversible ATP competitive inhibitor with Ki=1 nM. ARRY334543 is an AKT pathway inhibitor that inhibits cells with active ErbB-2 receptors. ARRY334543 acts on human cancer cells, such as BT-474 cells overexpressing ErbB-2 and A431 cells overexpressing ErbB-1, inhibiting ErbB-2 and ErbB-1 phosphorylation with IC50 of 43 nM and 36 nM, respectively.

 

In Vivo: Oral treatment of ARRY334543 inhibited tumor growth in human grafts that overexpressed ErbB-1(A431) or ErbB-2(MDA-MB-453) in a dose-dependent manner. ARRY334543 was administered orally to transplanted tumor mice that overexpressed tumor A431 and treated every other day for 21 days, and ARRY334543 significantly inhibited tumor growth. ARRY334543 has very good PK/ADME characteristics, It is highly active in mice carrying transplanted tumors such as epidermal carcinoma (A431), thymus carcinoma (BT-474, MDA-MB-453), non-small cell lung cancer (H1650,A549,292), colorectal cancer (Lovo,HT-29), and gastric cancer (N87). ARRY334543 was administered at 100 mg/kg/ day and 200 mg/kg/ day in BT-474 model, and the tumor growth inhibition rates were 69% and 98%, respectively. ARRY334543 is also effective in SK-OV-3 ovarian cancer model. ARRY334543 acts on BT-474 model and has very high activity.

 

Boiling Point: 637.1±65.0 °C at 760 mmHg

 

Flash Point: 339.1±34.3 °C

 

pKa: 6.54±0.70(Predicted)

 

Solubility: Soluble in DMSO. Insoluble in Water; insoluble in Ethanol.

 

GHS: GHS07, GHS09

 

Isomeric SMILES: C[C@@H]1COC(=N1)NC2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=NC=CS5)Cl  

 

InChIKey: UWXSAYUXVSFDBQ-CYBMUJFWSA-N  

 

InChI: InChI=1S/C22H19ClN6O2S/c1-13-10-31-22(27-13)29-14-2-4-18-16(8-14)21(26-12-25-18)28-15-3-5-19(17(23)9-15)30-11-20-24-6-7-32-20/h2-9,12-13H,10-11H2,1H3,(H,27,29)(H,25,26,28)/t13-/m1/s1

 

Attribute
[Chem Name]	4-N-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-N-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine
[Synonym]	Varlitinib; ARRY334543
[CAS No.]	845272-21-1
[MDL No.]	MFCD20275099
[Formula]	C22H19ClN6O2S
[Molecular]	466.94
[Form]	Solid Powder
[Storage]	Store at -20°C

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