Chemical Property of ABT-199
Chemical Property:
- PKA:4.09±0.10(Predicted)
- PSA：183.09000
- Density:1.340±0.06 g/cm3(Predicted)
- LogP:10.73070
- Storage Temp.:-20°C Freezer
- Solubility.:DMSO (Slightly)
- Purity/Quality:
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99% *data from raw suppliers
ABT199(Venetoclax) *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
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Description
ABT-199, also known as venetoclax, is a small, oral chemical molecule used for the treatment of chronic lymphocytic leukemia (CLL) associated with a specific chromosomal abnormality. As a second line treatment drug of CLL, ABT-199 take effects through acting as a BH3-mimetic and inhibitor of Bcl-2 (the anti-apoptotic B-cell lymphoma-2protein), further inducing apoptosis of CLL cells but not platelets. It also has the potential for the treatment of ER-positive breast cancer. Venetoclax, codeveloped by
AbbVie (previously Abbott Laboratories) and Genentech/
Roche, was approved in the US for treatment of patients with
chronic lymphocytic leukemia (CLL). To meet qualifications
for venetoclax treatment, patients must have received prior
therapy and possess the 17p deletion genetic mutation, as
determined by USFDA testing. Venetoclax functions as a
selective inhibitor of B cell lymphoma subtype 2 (BCL-2),
which is often overexpressed on malignant cells and thus leads
to impairment of the apoptotic pathway. Along these lines,
the orally dosed small molecule drug restores the ability of
malignant cells to undergo apoptosis as its mechanism of
action.90 Although other BCL-2 inhibitors are known, development
of similar agents such as navitoclox have been pursued
and halted due to undesired inhibition of BCL-XL, leading to
significant thrombocytopenia and demonstrating the need for
more selective inhibitors. Venetoclax is also currently being
considered for approval in Europe and Canada for similar
indications and is in various stages of development for the
treatment of non-Hodgkin lymphomas (NHL), acute myeloid
leukemia (AML), multiple myeloma (MM), and several other
disorders, either as a combination therapy or a stand-alone
treatment.
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Uses
ABT 199 (>99%) is a potent and selective BCL-2 inhibitor that achieves potent antitumour activity while sparing platelets. It’s practical application is to treat chronic lymphocytic leukaemic cells and estrogen receptor-positive breast cancer.
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Clinical Use
Selective inhibitor of B-cell lymphoma protein: Treatment of chronic lymphocytic leukaemia
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Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: concentration possibly increased by
ciprofloxacin, clarithromycin and erythromycin -
reduce venetoclax dose; avoid with rifampicin.
Anticoagulants: avoid with dabigatran; concentration
of warfarin increased.
Antidepressants: avoid with St John’s wort.
Antiepileptics: concentration possibly reduced by
carbamazepine, fosphenytoin and phenytoin - avoid.
Antifungals: concentration possibly increased by
fluconazole, itraconazole, ketoconazole, posaconazole
and voriconazole - reduce venetoclax dose.
Antipsychotics: increased risk of agranulocytosis
with clozapine - avoid.
Antivirals: concentration possibly reduced by
efavirenz and etravirine - avoid; concentration
possibly increased by ritonavir - reduce venetoclax
dose.
Bosentan: concentration of venetoclax possibly
reduced by bosentan - avoid.
Calcium channel blockers: concentration possibly
increased by diltiazem and verapamil - reduce
venetoclax dose.
Cardiac glycosides: avoid with digoxin.
Cytotoxics: avoid with everolimus.
Grapefruit juice: avoid concomitant use.
Modafinil: concentration of venetoclax possibly
reduced - avoid.
Sirolimus: avoid concomitant use.
Vaccines: avoid with live vaccines.
