生物活性

• 靶点	Bcl-2 Ki:0.01nM

• 描述Bcl-2 (B-cell lymphoma 2) is the first identified apoptotic regulator. It belongs to Bcl-2 family commitment to PCD, which regulates apoptosis, pro-apoptosis or anti-apoptosis. ABT-199 is a highly potent inhibitor of Bcl-2, re-engineered from ABT-263. It has subnanomolar affinity (Ki<0.010 nM, analysis by TR–FRET assay), which is over three orders of magnitude to Bcl-XL (Ki=48nM) and Bcl-W (Ki=245 nM). ABT-199 can disrupt BCL-2–BIM complex and induce multiple hallmarks of apoptosis, including cytochrome c release, caspase activation, the externalization of phosphatidylserine and the accumulation of sub-G0/G1 DNA, with lower concentration than ABT-263. Thus it facilitates ABT-199 to have cell-killing activity to Bcl-2 high-expressed NHL cell lines. ABT-199 can inhibit tumor xenograft growth as a single agent or combination with rituximab and bendamustine.^[1]
• 作用机制ABT-199 is complicated by the high degree of similarity within the BH3-binding domains of Bcl-2 and Bcl-XL.^[1]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  ALL-SIL	10 μM	Growth Inhibition Assay	48 h	IC50=0.1803 μM	25301704
  CCRF-CEM	10 μM	Growth Inhibition Assay	48 h	IC50=1.360 μM	24342948
  CS-THL1	20 nM	Growth Inhibition Assay	72 h	Inhibits cell growth assessed by cell viability	25916698

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• 动物研究
  剂量	Mice: max = 100 mg/kg[3]
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03342144	-	-	Recruiting	December 31, 2020	Germany ... more >> Onkologische Praxis /ID# 201545 Recruiting Stuttgart, Baden-Wuerttemberg, Germany, 70174 Medizinisches Versorgungszentrum (MVZ) /ID# 201548 Recruiting Aschaffenburg, Bayern, Germany, 63739 Studienzentrum Aschaffenburg /ID# 204125 Recruiting Aschaffenburg, Bayern, Germany, 63739 Praxis Dres. Hornberger & Kollegen /ID# 202613 Recruiting Bad Reichenhall, Bayern, Germany, 83435 Onkologie am Segelfliegerdamm /ID# 202603 Recruiting Berlin, Bayern, Germany, 12487 Onkologie Hof /ID# 201531 Recruiting Hof, Bayern, Germany, 95028 Praxis Dr. Vehling-Kaiser /ID# 202614 Recruiting Landshut, Bayern, Germany, 84028 Praxis Dres. Grüner/Hejazi/Niewenhuys /ID# 202602 Recruiting Weiden i.d.OPf., Bayern, Germany, 92637 Praxis Dr. Kreher /ID# 202604 Recruiting Bad Liebenwerda, Brandenburg, Germany, 04924 MVZ Dres. Cordes & Partner /ID# 202598 Recruiting Frankfurt am Main, Hessen, Germany, 60596 OAZ Hannover /ID# 201538 Recruiting Hanover, Niedersachsen, Germany, 30171 Onkolologische Praxis Oldenburg /ID# 202607 Recruiting Oldenburg, Niedersachsen, Germany, 26121 MVZ der Paracelsus-Klinik /ID# 201541 Recruiting Osnabrück, Niedersachsen, Germany, 49076 Med. Studiengesellschaft Nord West GmbH /ID# 201535 Recruiting Westerstede, Niedersachsen, Germany, 26655 Onkozentrum Dresden /ID# 202599 Recruiting Dresden, Sachsen, Germany, 01127 BAG Freiberg-Richter /ID# 201532 Recruiting Dresden, Sachsen, Germany, 01307 Onkologische Schwerpunktpraxis /ID# 200953 Recruiting Berlin, Germany, 10707 Internistische Schwerpunktprax /ID# 200949 Recruiting Erlangen, Germany, 91052 Luebecker Oncology Practice /ID# 200952 Recruiting Luebeck, Germany, 23562 Stauferklinikum Schwaebisch Gm /ID# 201518 Recruiting Mutlangen, Germany, 73557 Collapse <<
  NCT03112174	Mantle-Cell Lymphoma	Phase 3	Recruiting	September 2022	-
  NCT03672695	Acute Myeloid Leukaemia	Phase 1	Not yet recruiting	March 31, 2022	United States, Connecticut ... more >> Smilow Cancer Hospital at Yale Not yet recruiting New Haven, Connecticut, United States, 06511 United States, Texas The University of Texas MD Anderson Cancer Center, Houston, TX Not yet recruiting Houston, Texas, United States, 77030 Australia Peter MacCallum cancer centrer Not yet recruiting Melbourne, Australia The Alfred Hospital Department of Haematology Not yet recruiting Victoria Park, Australia France Institut Paoli-Calmettes Not yet recruiting Marseille, France Hopital Saint-Antoine Not yet recruiting Paris, France Institut Universitaire du Cancer Toulouse - Oncopole Not yet recruiting Toulouse, France Collapse <<

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• 参考文献

• [1] Souers AJ, Leverson JD, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.

  [2] Choo EF, Boggs J, et al. The role of lymphatic transport on the systemic bioavailability of the Bcl-2 protein family inhibitors navitoclax (ABT-263) and ABT-199. Drug Metab Dispos. 2014 Feb;42(2):207-12.

  [3] Punnoose EA, Leverson JD, et al. Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models. Mol Cancer Ther. 2016 May;15(5):1132-44.