ABT-199, BCL-2 inhibitor


Catalog No. size PriceQuantity
M60075-2D 10 mM DMSO (0.230 mL) $99
M60075-2S 2 mg solid $99
M60075-10S 10mg solid $401

Description

Product Information
Chemical Name: (4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide)
Molecular Weight: 868.44
Formula: C45H50ClN7O7S
Purity: ≥ 98%
CAS#: 1257044-40-8
Solubility: DMSO up to 50 mM
Storage: Powder: 4oC 1 year DMSO: 4oC 3 month -20oC 1 year



Biological Activity:

ABT-199 is a highly potent, selective, and orally bioavailable BCL-2 inhibitor. ABT-199 has picomolar affinity for BCL-2 (Ki < 0.010 nM) and > 1000 folds selectivity over BCL-XL (Ki = 48 nM) and BCL-W (Ki = 245 nM). Therefore, ABT-199 is a much improved lead compound over the original ABT-263 (navitoclax) to avoid thrombocytopenia caused by BCL-XL inhibition. ABT-199’s cell-killing effect is selective and mechanism dependent. It can potently kill BCL-2-overexpressing FL5.12 cells (EC50 ~ 4 nM) and RS4;11 BCL-2–dependent ALL cells (EC50 ~8 nM), but showed much weaker activity against BCL-XL-overexpressing FL5.12 cells (EC50 ~261 nM) and H146 ALL cells (EC50 ~4,260 nM). ABT-199 inhibits the growth of BCL-2–dependent human hematological tumors in vivo and spares human platelets as a single agent or in combination with rituximab and bendamustine. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicates that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2–dependent hematological cancers.


How to Use:

In vitro: ABT-199 was used at 0.1-1 ¦ÌM final concentration in vitro and in cellular assays.

In vivo: ABT-199 was orally dosed to mice at 12.5-100 mg/kg once per day in combination with rituximab and Bendamustine, and significantly reduced tumor volume.


Reference:

    1. Fresquet V, et al. Acquired mutations in BCL2 family proteins conferring resistance to the BH3 mimetic ABT-199 in lymphoma. (2014) Blood. 123(26):4111-9.
    2. Souers AJ, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. (2013) Nat Med. 19(2):202-8.
    3. Roberts, A.W. et al. Selective inhibition of BCL-2 is active against chronic lymphocytic leukemia (CLL): first clinical experience with the BH3-mimetic ABT-199. Abstract 546 (European Hematology Association 2012, Amsterdam, The Netherlands, June 14¨C17, 2012).


        Products are for research use only. Not for human use.

        Payment & Security

        American Express Apple Pay Diners Club Discover Elo Google Pay JCB Mastercard PayPal Shop Pay Venmo Visa

        Your payment information is processed securely. We do not store credit card details nor have access to your credit card information.

        Estimate shipping

        You may also like

        Recently viewed