ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim), leading to the initiation of apoptosis within 2 hours posttreatment. In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis.

How does Navitoclax work?

Navitoclax targets the Bcl-2 family of proteins, the major negative regulators of apoptosis. The Bcl-2 proteins, including Bcl-2, Bcl-xL, and Bcl-w, work by binding to two other groups of proteins-the executioners (Bax, Bak) that actually start the destruction pathway, and the sentinel proteins.

What does Navitoclax treat?

Navitoclax alone potently treats small cell lung cancer and acute lymphocytic leukemia, whilst in combination therapy for solid tumors, it enhances the therapeutic effect of other chemotherapeutic agents.

Who makes Navitoclax?

Navitoclax is an orally available small molecule inhibitor of the Bcl-2 family of proteins, being developed by AbbVie, for the treatment of myelofibrosis, colorectal cancer, Crohn’s disease, head and neck cancer and idiopathic pulmonary fibrosis.

What gene is overexpressed in lymphoma?

Amplification of the MDM2 gene was found in more than a third of sarcomas and in a subset of malignant gliomas. Despite the absence of amplification, the MDM2 gene was overexpressed in some types of leukemias and lymphomas.

How long do you take Venclexta?

You will continue to take VENCLEXTA once daily until the end of the 12-month treatment period. VENCLEXTA should be taken at the recommended daily dose as prescribed until your healthcare provider tells you to stop taking VENCLEXTA or changes your dose.

How does BH3 mimetic work?

BH3 mimetics are small molecules that mimic BH3-proteins by binding to anti-apoptotic BCL-2 family proteins. To date, more than 20 compounds have been identified, and their effects in cancer therapy have been analyzed.

What is Lymphomatoid granulomatosis?

Lymphomatoid granulomatosis is a rare disorder characterized by overproduction (proliferation) of white blood cells called lymphocytes (lymphoproliferative disorder). The abnormal cells infiltrate and accumulate (form lesions or nodules) within tissues.

What is the mechanism of action of ABT-263?

In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia.

What is navnavitoclax (ABT-263)?

Navitoclax (ABT-263) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, but binds more weakly to Mcl-1 and A1. Phase 2. ABT-263 is structurally related to ABT-737; it is a disruptor of Bcl-2/Bcl-xL interactions with pro-apoptotic proteins.

What is the oral bioavailability of ABT-263?

The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim), leading to the initiation of apoptosis within 2 hours posttreatment.

What is the EC50 value of ABT-263?

ABT-263 displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. [1]