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1033808-28-4

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1033808-28-4 Usage

Check Digit Verification of cas no

The CAS Registry Mumber 1033808-28-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,3,3,8,0 and 8 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1033808-28:
(9*1)+(8*0)+(7*3)+(6*3)+(5*8)+(4*0)+(3*8)+(2*2)+(1*8)=124
124 % 10 = 4
So 1033808-28-4 is a valid CAS Registry Number.

1033808-28-4Upstream product

1033808-28-4Downstream Products

1033808-28-4Relevant articles and documents

Design and synthesis of pyrrolo[3,2- d ]pyrimidine human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors: Exploration of novel back-pocket binders

Kawakita, Youichi,Banno, Hiroshi,Ohashi, Tomohiro,Tamura, Toshiya,Yusa, Tadashi,Nakayama, Akiko,Miki, Hiroshi,Iwata, Hidehisa,Kamiguchi, Hidenori,Tanaka, Toshimasa,Habuka, Noriyuki,Sogabe, Satoshi,Ohta, Yoshikazu,Ishikawa, Tomoyasu

, p. 3975 - 3991 (2012)

To develop novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) kinase inhibitors, we explored pyrrolo[3,2-d]pyrimidine derivatives bearing bicyclic fused rings designed to fit the back pocket of the HER2/EGFR proteins. Among them, the 1,2-benzisothiazole (42m) ring was selected as a suitable back pocket binder because of its potent HER2/EGFR binding and cell growth inhibitory (GI) activities and pseudoirreversibility (PI) profile as well as good bioavailability (BA). Ultimately, we arrived at our preclinical candidate 51m by optimization of the N-5 side chain to improve CYP inhibition and metabolic stability profiles without a loss of potency (HER2/EGFR inhibitory activity, IC50, 0.98/2.5 nM; and GI activity BT-474 cells, GI50, 2.0 nM). Reflecting the strong in vitro activities, 51m exhibited potent tumor regressive efficacy against both HER2- and EGFR-overexpressing tumor (4-1ST and CAL27) xenograft models in mice at oral doses of 50 mg/kg and 100 mg/kg.

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