生物活性

• 靶点	TNFα IC50:13nM

• 描述Cereblon, encoded by CRBN gene, is the substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Cereblon, or the E3 ligase complex mediated normal degradation of key regulatory proteins is required for multiple biological processes, such as normal limb outgrowth. It is well reported that binding of thalidomide-related drugs, such as Lenalidomide, changes the substrate specificity of the E3 ligase complex, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3^[5]. Pomalidomide is an analogue of thalidomide. The cellular target of pomalidomide is cereblon. In a fluorescence thermal melt assay utilizing recombinant CRBN (cereblon), it was revealed that pomalidomide bound to cereblon^[6]. Pomalidomide increased HbF production in human erythroid cells at the concentration of 1 μM. After incubation for 6 days, pomalidomide induced 2-fold upregulation of γ-globin mRNA levels while decreased β-globin levels 2-fold, also at the concentration of 1 μM^[7]. According to another report, pomalidomide was used at the concentrations between 1 nM and 10 μM in both CD4+ and CD8+ cells, pomalidomide significantly elevated IL-2, IL-5, IL-10, and IFN-γSchafer PH, Gandhi AK, Loveland MA, Chen RS, Man HW, Schnetkamp PP, Wolbring G, Govinda S, Corral LG, Payvandi F, Muller GW, Stirling DI. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 Jun;305(3):1222-32. doi: 10.1124/jpet.102.048496. Epub 2003 Mar 20. PMID: 12649301.|. 8 doses of pomalidomide i.p. administrated at the dose of 0.5 mg/kg among a period of 19 days significantly enhanced the antitumor activity of rituximab in a disseminated lymphoma-bearing SCID mice xenograft model established by i.v. injection of Raji cells. The median survival time of animals treated with pomalidomide and rituximab was 74 days compared to 38 days of those treated with rituximab monotherapy, while pomalidomide was not effective as a single agent^[8].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  APK-1	39-1250 nM	Growth Inhibition Assay	5 d	IC50=226 nM, inhibits cell viability dose dependently	26119939
  BC-1	39-1250 nM	Growth Inhibition Assay	5 d	IC50=744 nM, inhibits cell viability dose dependently	26119939
  BC-3	39-1250 nM	Growth Inhibition Assay	5 d	IC50=107 nM, inhibits cell IC50=107 nM, viability dose dependently	26119939

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• 动物研究
  剂量	Mice: 50 mg/kg[3] (p.o.); 7 mg/kg[4] (i.p.)
  给药途径	p.o., i.p.
  动物药代数据	Animal Rats[3] Dose 5 mg/kg (i.v.) 50 mg/kg (p.o.) Administration i.v. p.o. AUCinf 7016 ± 1551 ng·h/ml (i.v.) Vd 1.75 ± 0.2 L/kg (i.v.) T1/2 2.44 ± 0.8 h (i.v.) Brain: blood 0.39 ± 0.03 Tmax 4.1 ± 1.5 h (p.o.) CL 12.3 ± 2.6 ml/min/kg (i.v.) Cmax 430.0 ± 63 ng/ml (p.o.) AUC0-10 2700 ± 740 ng·h/ml (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
  NCT01745640	Multiple Myeloma	Phase 2	Completed	-	France ... more >> CHRU-Hôpital Sud Amiens Amiens, France, 80054 Chru Caen Caen, France, 14033 CHU DIJON, Hôpital d'Enfants Dijon, France, 21000 CHRU, Hôpital A.Michallon Grenoble, France, 38043 Centre hospitalier départemental La Roche sur Yon La Roche sur Yon, France, 85025 Chru Lille Lille, France, 59037 Institut Paoli Calmette, Marseille, France, 13273 CHRU, Hôtel Dieu Nantes, France, 44035 Hôpital Saint-Louis Paris, France, 75475 CHU - Hôpital St Antoine, Paris, France, 75571 Hôpital Haut-Leveque PESSAC cedex, France, 33604 Centre Hospitalier Lyon Sud -1 Pierre Benite, France, 69495 Centre Hospitalier Lyon Sud -2 Pierre Benite, France, 69495 CHRU POITIERS-Hôpital Jean Bernard Poitiers, France, 86021 Hôpital Robert Debré, CHU Reims Reims, France, 51092 CHRU RENNES 2, Hôpital Pontchaillou Rennes, France, 35033 CHRU RENNES 1, Hôpital Sud Rennes, France, 35056 CHRU, Hôpital Purpan Toulouse, France, 31059 CHRU- Hôpital Bretonneau Tours, France, 37044 CHRU, Hôpitaux de Brabois Vandoeuvre, France, 54511 Collapse <<
  NCT03227432	Multiple Myeloma	Phase 2	Withdrawn(Withdrawn before enr... more >>ollment due to issues around the FDA hold on PD-1/PD-L1 drugs in combination with IMIDs.) Collapse <<	December 31, 2024	United States, Massachusetts ... more >> Massachusetts General Hospital Boston, Massachusetts, United States, 02114 Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02115 Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 Collapse <<
  NCT02654132	Multiple Myeloma	Phase 2	Active, not recruiting	April 22, 2019	-

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