Venetoclax

Venetoclax is a pivotal active pharmaceutical ingredient (API) and research compound in the treatment of hematological malignancies, most notably chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). As a highly selective BCL‑2 inhibitor, Venetoclax mimics the action of BH3‑only proteins—the native ligands of BCL‑2—by binding to the hydrophobic groove of BCL‑2 proteins, thereby repressing BCL‑2 activity and restoring apoptotic processes in tumor cells. Venetoclax has demonstrated remarkable clinical efficacy as a monotherapy and in combination with agents such as rituximab and obinutuzumab for patients with refractory or relapsed CLL. In addition to its approved indications, Venetoclax is under active investigation for multiple myeloma, diffuse large B‑cell lymphoma, and other BCL‑2‑dependent cancers, underscoring the broad therapeutic potential of this groundbreaking targeted therapy.

 

Product Parameters

---

Parameter	Specification
Product Name	Venetoclax
CAS Number	1257044-40-8
Molecular Formula	C₄₅H₅₀ClN₇O₇S
Molecular Weight	868.44 g/mol
Appearance	Yellow solid
Melting Point	＞150 ℃
pKa	4.09±0.10
Density	1.340 ± 0.06 g/cm³
Storage Condition	−20 °C

 

Bioactivity

---

ABT-199 (GDC-0199) is a selective Bcl-2 inhibitor with a Ki value of <0.01 nM in cell-free assays, exhibiting over 4,800-fold higher selectivity for Bcl-xL and Bcl-w compared to Bcl-xL and Bcl-w, while showing no inhibitory activity against Mcl-1.

 

In Vitro S tudy

---

ABT-199 exhibits low sensitivity to Bcl-xL, Mcl-1, and Bcl-w, with Ki values of 48 nM,>444 nM, and 245 nM, respectively. It effectively inhibits FL5.12-Bcl-2 cells and RS4;11 cells at EC50 values of 4 nM and 8 nM, respectively, but demonstrates low activity against FL5.12-Bcl-xL cells with an EC50 of 261 nM. ABT-199 induces rapid apoptosis in RS4;11 cells, accompanied by cytochrome c release, caspase activation, phosphatidylserine translocation, and sub-G0/G1 phase DNA accumulation. Quantitative immunoblotting results demonstrate that the sensitivity of ABT-199 to cell lines including NHL, DLBCL, MCL, AML, and ALL is strongly correlated with Bcl-2 expression levels. ABT-199 also induces apoptosis in CLL cells, with an average EC50 of 3.0 nM.

 

In Vivo Studies

---

ABT-199 (100 mg/kg) treatment of RS4;11 transplanted tumors achieved a maximum tumor growth inhibition rate of 95%, with tumor growth delayed by 152% (Chemical Book). ABT-199, either administered alone or in combination with SDX-105 and other agents, also inhibited tumor growth in DoHH2 and Granta-519 transplanted tumors.

 

Contact Us

---

Need Venetoclax for your API manufacturing campaign, research program, or ANDA filing? Cosperpharm makes it simple. Reach out to our team today for pricing, documentation, and technical support.