A-1155463 Struktur

A-1155463

Bezeichnung:A-1155463

CAS-Nr1235034-55-5

Englisch Name:A-1155463

CBNumberCB13066996

SummenformelC35H32FN5O4S2

Molgewicht669.79

MOL-Datei1235034-55-5.mol

A-1155463 physikalisch-chemischer Eigenschaften

Dichte	1.45±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
Löslichkeit	≥67 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
Aggregatzustand	solid
pka	1.11±0.36(Predicted)
Farbe	Off-white to yellow

Gefahreninformationscode (GHS)

A-1155463 Chemische Eigenschaften,Einsatz,Produktion Methoden

Verwenden
A-1155463 Hydrochloride, is a potent and selective BCL-XL inhibitor with in vivo activity. A-1155463 is a proteolytically stable, cell-permeable and high affinity BH3 mimetic Ligand of BCL protein BCL-XL, binding to the target potently and selectively with a Ki value of <0.01nM (<10 pM), highly selective against closely related proteins of BCL-2 (Ki = 74nM, >7000-fold selectivity), BCL-W (Ki = 8 nM, >800-fold selectivity), and MCL-1 (Ki >444nM, >40000-fold selectivity). A-1155463, together with A-1331852 , represent the first-in-class small molecule BCL-XL selective inhibitors achieving clear-on-target in vivo activity with high potency and selectivity. In living cells, A-1155463, as anticipated, experts an effort to disrupt the tight-binding BCL-XL-BIM, but not BCL-2–BIM, complexes, killi
Biologische Aktivität
ki=19 nma-1155463 is a potent and selective bcl-xl inhibitor.bcl-2 plays a key role in the survival of lymphoid malignancies, while bcl-xl overexpression has been associated with drug resistance and disease progression of various solid tumors and hematological malignancies.
in vitro
a-1155463 was identified via nuclear magnetic resonance fragment screening and structure-based design to be a highly potent and selective bcl-xl inhibitor. a-1155463 was found to be substantially more potent against bcl-xl-dependent cell lines relative to the previously reported inhibitor, wehi-539 [1].
in vivo
animal study showed that following a single ip dose of a-1155463 at 5 mg/kg in nontumor bearing scid-beige mice, platelet counts dramatically decreased at 6 h postdose and then rebounded to normal levels within 72 h. such platelet depletion and recovery kinetics were similar to those of the dual inhibitor navitoclax. moreover, in order to give additional evidence that a-1155463 was conferring on-target in-vivo activity, a-1155463 was then administered to scidbeige mice that had been inoculated with bcl-xl-dependent h146 tumor cells. results showed that the daily ip dosing of a-1155463 at 5 mg/kg for 14 days caused a statistically significant inhibition of tumor growth, which was alleviated upon cessation of dosing [1].
target

Target Value
BCL-XL
(Cell-free assay) <0.01 nM(Ki)
Einzelnachweise
[1] tao zf et al. discovery of a potent and selective bcl-xl inhibitor with in vivo activity. acs med chem lett. 2014 aug 26;5(10):1088-93.

A-1155463 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Send Inquriy

Target	Value
BCL-XL (Cell-free assay)	<0.01 nM(Ki)