Lenalidomide hydrochloride

CAS: 1243329-97-6 F: C13H14ClN3O3 W: 295.72

Lenalidomide hydrochloride (CC-5013 hydrochloride), a derivative of Thalidomide, acts as molecular glue. Lenalidomide hy

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Bioactivity	Lenalidomide hydrochloride (CC-5013 hydrochloride), a derivative of Thalidomide, acts as molecular glue. Lenalidomide hydrochloride is an orally active immunomodulator. Lenalidomide hydrochloride (CC-5013 hydrochloride) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide hydrochloride (CC-5013 hydrochloride) specifically inhibits growth of mature B-cell lymphomas, including multiple myeloma, and induces IL-2 release from T cells[1][2].
Invitro	Lenalidomide is potent in stimulating T cell proliferation and IFN-γ and IL-2 production. Lenalidomide has been shown to inhibit production of pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 and elevate the production of anti-inflammatory cytokine IL-10 from human PBMCs. Lenalidomide downregulates the production of IL-6 directly and also by inhibiting multiple myeloma (MM) cells and bone marrow stromal cells (BMSC) interaction, which augments the apoptosis of myeloma cells[2]. Dose-dependent interaction with the CRBN-DDB1 complex is observed with Thalidomide, Lenalidomide and Pomalidomide, with IC50 values of ~30 μM, ~3 μM and ~3 μM, respectively, These reduced CRBN expression cells (U266-CRBN60 and U266-CRBN75) are less responsive than the parental cells to antiproliferative effects Lenalidomide across a dose-response range of 0.01 to 10 μM[3]. Lenalidomide, a thalidomide analog, functions as a molecular glue between the human E3 ubiquitin ligase cereblon and CKIα is shown to induce the ubiquitination and degradation of this kinase, thus presumably killing leukemic cells by p53 activation[5].
In Vivo	The toxicity of Lenalidomide doses up to 15, 22.5, and 45 mg/kg via IV, IP, and PO routes of administration. Limited by solubility in our PBS dosing vehicle, these maximum achievable Lenalidomide doses are well tolerated with the exception of one mouse death (of four total dosed) at the 15 mg/kg IV dose. Notably, no other toxicities are observed in the study at IV doses of 15 mg/kg (n=3) or 10 mg/kg (n=45) or at any other dose level through IV, IP, and PO routes[4].
Name	Lenalidomide hydrochloride
CAS	1243329-97-6
Formula	C13H14ClN3O3
Molar Mass	295.72
Transport	Room temperature in continental US; may vary elsewhere.
Storage	Please store the product under the recommended conditions in the Certificate of Analysis.
Reference	[1]. Omran A, et al. Effects of MRP8, LPS, and lenalidomide on the expressions of TNF-α , brain-enriched, and inflammation-related microRNAs in the primary astrocyte culture. ScientificWorldJournal. 2013 Sep 21;2013:208309. [2]. Krönke J, et al. Lenalidomide induces degradation of IKZF1 and IKZF3. Oncoimmunology. 2014 Jul 3;3(7):e941742. [3]. Minzel W, et al. Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Cell. 2018 Sep 20;175(1):171-185.e25. [4]. Kotla V, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009 Aug 12;2:36. [5]. Lopez-Girona A, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012 Nov;26(11):2326-35. [6]. Rozewski DM, et al. Pharmacokinetics and tissue disposition of lenalidomide in mice. AAPS J. 2012 Dec;14(4):872-82.