拉泽替尼, 表皮生长因子受体 erbB1 抑制剂

小分子

CCG-270023 | Leclaza | RRMJMHOQSALEJJ-UHFFFAOYSA-N | (E)-(3R,5S)-7-[3-(4-Fluoro-phenyl)-1-isopropyl-1H-indol-2-yl]-3,5-dihydroxy-hept-6-enoic acid | Lazertinib (YH25448) | N-[5-[[4-[4-[(dimethylamino)methyl]-3-phenylpyrazol-1-yl]pyrimidin-2-yl]amino]-4-me

Lazertinib

L422330-1ml

1ml

Moligand™

2mM in DMSO

-80℃储存

超低温冰袋运输

Information Lazertinib (YH25448,GNS-1480) is a potent, highly mutant-selective and irreversibleEGFR-TKIwith IC50 values of 1.7 nM, 2 nM, 5 nM, 20.6 nM and 76 nM for Del19/T790M, L858R/T790M, Del19, L85R and Wild type EGFR respectively, showing much higher IC50 values aganist ErbB2 and ErbB4. Targets Del19/T790M (Cell-free assay); L858R/T790M EGFR (Cell-free assay); Del19 (Cell-free assay); L85R (Cell-free assay); WT EGFR (Cell-free assay) 1.7 nM; 2 nM; 5 nM; 20.6 nM; 76 nM In vitro Lazertinib targets the activating EGFR mutations Del19 and L858R, as well as the T790M mutation, while sparing wild type. In NSCLC cell lines and primary cancer cells from patients harboring EGFR mutations, YH25448 more potently inhibits cancer cell growth and significantly increases tumor cell apoptosis compared to osimertinib. In the cell proliferation assays, GI50 values of lazertinib are 6 nM, 5 nM, and 711 nM for H1975 cells (L858R/T790M), PC9 cells (del19) and H2073 cells (wt), respectively. In vivo In an in vivo mouse model implanted with H1975 cells, once-daily YH25448 treatment results in indramatic dose-dependent tumor regression in both subcutaneous and intracranial lesions with no abnormal signs such as skin keratosis. The plasma half-life of YH25448 is 5.9-6.8 hr, while the tumor to plasma AUC 0-last ratio is 3.0-5.1 in tumor-bearing mice. YH25448 shows excellent penetration of the blood-brain bartier, achieving CSF concentrations exceeding the IC50 value for pEGFR inhibition. YH25448 shows superior efficacy for tumor regression in an EGFR mutant brain metastasis model. Cell Research(from reference) Cell lines：Ba/F3 cells Concentrations：5, 10, 100 nM Incubation Time：6 h

拉唑替尼（YH25448,GNS-1480）是一种强效、高突变选择性和不可逆的表皮生长因子受体-TKI，对 Del19/T790M、L858R/T790M、Del19、L85R 和野生型表皮生长因子受体的 IC50 值分别为 1.7 nM、2 nM、5 nM、20.6 nM 和 76 nM，对 ErbB2 和 ErbB4 的 IC50 值更高。

1903008-80-9

C30H34N8O3

554.64 g/mol

121269225

CN(C)CC1=CN(N=C1C2=CC=CC=C2)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N5CCOCC5)OC

N-[5-[[4-[4-[(dimethylamino)methyl]-3-phenylpyrazol-1-yl]pyrimidin-2-yl]amino]-4-methoxy-2-morpholin-4-ylphenyl]prop-2-enamide

1S/C30H34N8O3/c1-5-28(39)32-23-17-24(26(40-4)18-25(23)37-13-15-41-16-14-37)33-30-31-12-11-27(34-30)38-20-22(19-36(2)3)29(35-38)21-9-7-6-8-10-21/h5-12,17-18,20H,1,13-16,19H2,2-4H3,(H,32,39)(H,31,33,34)

RRMJMHOQSALEJJ-UHFFFAOYSA-N

CN(C)CC1=CN(N=C1C2=CC=CC=C2)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N5CCOCC5)OC

2

9

10

554.275 Da

554.275 Da

110.000 Ų

41

0

837

0

1

3.4

4.56

L858R/T790M EGFR, IC50: 2 nM; WT EGFR, IC50: 76 nM

29384987

抑制剂

表皮生长因子受体 erbB1 抑制剂

4

7.211849299

＜1

6

2

10