WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205878
CAS#: 664334-36-5
Description: Motixafortide, also known as BL-8040, BKT140 and TF 14016, is an orally bioavailable inhibitor of CXC Chemokine Receptor 4 (CXCR4) with potential antineoplastic activity. CXCR4 antagonist BKT140 selectively binds to the chemokine receptor CXCR4, preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation, which may result in decreased tumor cell proliferation and migration. In addition, inhibition of CXCR4 may induce mobilization of hematopoietic cells from the bone marrow into blood. The G protein-coupled receptor CXCR4 plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types; SDF-1/CXCR4 interaction induces retention of hematopoietic cells in the bone marrow.
Hodoodo Cat#: H205878
Name: Motixafortide
CAS#: 664334-36-5
Chemical Formula: C97H144FN33O19S2
Exact Mass: 2,158.07
Molecular Weight: 2,159.549
Elemental Analysis: C, 53.95; H, 6.72; F, 0.88; N, 21.40; O, 14.08; S, 2.97
Synonym: BKT140; BKT 140; BKT-140; BL8040; BL 8040; BL-8040. TN-14003; 4F-Benzoyl-TN14003; TF 14016; TF14016; TF-14016. Motixafortide; BKT140 (4-fluorobenzoy); {4-Fluorobenzoyl}-Arg-Arg-{2-Naph-Ala}-Cys-Tyr-{Cit}-Lys-{d-Lys}-Pro-Tyr-Arg-{Cit}-Cys-Arg-NH2 (Disulfide bridge: Cys4-Cys13)
IUPAC/Chemical Name: (3S,6S,9S,12R,17R,20S,23S,26S,29S,34aS)-N-((S)-1-amino-5-guanidino-1-oxopentan-2-yl)-26,29-bis(4-aminobutyl)-17-((S)-2-((S)-2-((S)-2-(4-fluorobenzamido)-5-guanidinopentanamido)-5-guanidinopentanamido)-3-(naphthalen-2-yl)propanamido)-6-(3-guanidinopropyl)-3,20-bis(4-hydroxybenzyl)-1,4,7,10,18,21,24,27,30-nonaoxo-9,23-bis(3-ureidopropyl)triacontahydro-1H,16H-pyrrolo[2,1-p][1,2]dithia[5,8,11,14,17,20,23,26,29]nonaazacyclodotriacontine-12-carboxamide
InChi Key: JJVZSYKFCOBILL-MKMRYRNGSA-N
InChi Code: InChI=1S/C97H144FN33O19S2/c98-60-33-31-58(32-34-60)78(135)119-65(19-8-42-113-93(104)105)79(136)121-68(21-10-44-115-95(108)109)83(140)126-73(51-56-25-30-57-14-1-2-15-59(57)48-56)87(144)130-75-53-152-151-52-74(88(145)118-63(77(101)134)18-7-41-112-92(102)103)129-84(141)69(23-12-46-117-97(111)150)122-81(138)66(20-9-43-114-94(106)107)124-86(143)72(50-55-28-37-62(133)38-29-55)128-90(147)76-24-13-47-131(76)91(148)70(17-4-6-40-100)125-82(139)64(16-3-5-39-99)120-80(137)67(22-11-45-116-96(110)149)123-85(142)71(127-89(75)146)49-54-26-35-61(132)36-27-54/h1-2,14-15,25-38,48,63-76,132-133H,3-13,16-24,39-47,49-53,99-100H2,(H2,101,134)(H,118,145)(H,119,135)(H,120,137)(H,121,136)(H,122,138)(H,123,142)(H,124,143)(H,125,139)(H,126,140)(H,127,146)(H,128,147)(H,129,141)(H,130,144)(H4,102,103,112)(H4,104,105,113)(H4,106,107,114)(H4,108,109,115)(H3,110,116,149)(H3,111,117,150)/t63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,74-,75-,76-/m0/s1
SMILES Code: O=C([C@@H](NC([C@H](CCCNC(N)=O)NC([C@H](CCCNC(N)=N)NC([C@H](CC1=CC=C(O)C=C1)NC([C@@](CCC2)([H])N2C([C@H](CCCCN)NC([C@H](CCCCN)NC([C@H](CCCNC(N)=O)NC([C@H](CC3=CC=C(O)C=C3)N4)=O)=O)=O)=O)=O)=O)=O)=O)CSSC[C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC(C5=CC=C(F)C=C5)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CC6=CC=C7C=CC=CC7=C6)=O)C4=O)N[C@@H](CCCNC(N)=N)C(N)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2933.99.79.00
More Info: BKT140, currently being developed by Biokine, is a highly selective inverse agonist of CXCR4, with a high affinity (0.8nM) and a low rate of dissociation from its receptor. Pre-clinical studies in animal models with BKT140 showed a robust mobilization of hematopoietic stem cells. Furthermore, BKT140 also showed a direct and indirect anti-tumor effect in vitro and in vivo against a variety of human-derived tumors, such as multiple myeloma, lymphoma, leukemia, neuroblastoma, retinoblastoma and lung cancer. BKT140 directly stimulates apoptosis (cell death) of certain types of tumors, interferes with CXCR4 mediated drug-resistance of tumor cells (CAM-DR), and enhances the therapeutic potential of anti-cancer drugs that fail to eliminate residual disease and cancer stem cells. (source: http://biokine.com/?p=17).
| Biological target: | Motixafortide (BKT140 4-fluorobenzoyl) is a novel CXCR4 antagonist with an IC50 vakue of ～1 nM. |
| In vitro activity: | Overexpression of CXCR4 or stimulation with CXCL12 supports neuroblastoma tumorigenesis. Moreover, CXCR4 inhibition with the high-affinity CXCR4 antagonist BL-8040 prevented tumor growth and reduced survival of tumor cells. Reference: Cancer Res. 2018 Mar 15;78(6):1471-1483. https://pubmed.ncbi.nlm.nih.gov/29259008/ |
| In vivo activity: | BL-8040 also synergized with FLT3 inhibitors to induce AML cell death. Importantly, this combined treatment prolonged the survival of tumor-bearing mice and reduced minimal residual disease in vivo. Reference: Leukemia. 2017 Nov;31(11):2336-2346. https://pubmed.ncbi.nlm.nih.gov/28280274/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 150.0 | 69.46 | |
| Water | 100.0 | 46.31 |
The following data is based on the product molecular weight 2,159.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Klein S, Abraham M, Bulvik B, Dery E, Weiss ID, Barashi N, Abramovitch R, Wald H, Harel Y, Olam D, Weiss L, Beider K, Eizenberg O, Wald O, Galun E, Pereg Y, Peled A. CXCR4 Promotes Neuroblastoma Growth and Therapeutic Resistance through miR-15a/16-1-Mediated ERK and BCL2/Cyclin D1 Pathways. Cancer Res. 2018 Mar 15;78(6):1471-1483. doi: 10.1158/0008-5472.CAN-17-0454. Epub 2017 Dec 19. PMID: 29259008. 2. Abraham M, Klein S, Bulvik B, Wald H, Weiss ID, Olam D, Weiss L, Beider K, Eizenberg O, Wald O, Galun E, Avigdor A, Benjamini O, Nagler A, Pereg Y, Tavor S, Peled A. The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression. Leukemia. 2017 Nov;31(11):2336-2346. doi: 10.1038/leu.2017.82. Epub 2017 Mar 10. PMID: 28280274. |
| In vitro protocol: | 1. Klein S, Abraham M, Bulvik B, Dery E, Weiss ID, Barashi N, Abramovitch R, Wald H, Harel Y, Olam D, Weiss L, Beider K, Eizenberg O, Wald O, Galun E, Pereg Y, Peled A. CXCR4 Promotes Neuroblastoma Growth and Therapeutic Resistance through miR-15a/16-1-Mediated ERK and BCL2/Cyclin D1 Pathways. Cancer Res. 2018 Mar 15;78(6):1471-1483. doi: 10.1158/0008-5472.CAN-17-0454. Epub 2017 Dec 19. PMID: 29259008. 2. Abraham M, Klein S, Bulvik B, Wald H, Weiss ID, Olam D, Weiss L, Beider K, Eizenberg O, Wald O, Galun E, Avigdor A, Benjamini O, Nagler A, Pereg Y, Tavor S, Peled A. The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression. Leukemia. 2017 Nov;31(11):2336-2346. doi: 10.1038/leu.2017.82. Epub 2017 Mar 10. PMID: 28280274. |
| In vivo protocol: | 1. Abraham M, Klein S, Bulvik B, Wald H, Weiss ID, Olam D, Weiss L, Beider K, Eizenberg O, Wald O, Galun E, Avigdor A, Benjamini O, Nagler A, Pereg Y, Tavor S, Peled A. The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression. Leukemia. 2017 Nov;31(11):2336-2346. doi: 10.1038/leu.2017.82. Epub 2017 Mar 10. PMID: 28280274. |
1: Beider K, Ribakovsky E, Abraham M, Wald H, Weiss L, Rosenberg E, Galun E, Avigdor A, Eizenberg O, Peled A, Nagler A. Targeting the CD20 and CXCR4 Pathways in Non Hodgkin Lymphoma with Rituximab and high affinity CXCR4 antagonist BKT140. Clin Cancer Res. 2013 May 10. [Epub ahead of print] PubMed PMID: 23637121.
2: Discussion. J Thorac Cardiovasc Surg. 2012 Nov;144(5):1175. doi: 10.1016/j.jtcvs.2012.07.048. Epub 2012 Aug 24. PubMed PMID: 22925569.
3: Fahham D, Weiss ID, Abraham M, Beider K, Hanna W, Shlomai Z, Eizenberg O, Zamir G, Izhar U, Shapira OM, Peled A, Wald O. In vitro and in vivo therapeutic efficacy of CXCR4 antagonist BKT140 against human non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012 Nov;144(5):1167-1175.e1. doi: 10.1016/j.jtcvs.2012.07.031. Epub 2012 Aug 24. PubMed PMID: 22925564.
4: de Nigris F, Schiano C, Infante T, Napoli C. CXCR4 inhibitors: tumor vasculature and therapeutic challenges. Recent Pat Anticancer Drug Discov. 2012 Sep;7(3):251-64. Review. PubMed PMID: 22376154.
5: Burger JA, Stewart DJ, Wald O, Peled A. Potential of CXCR4 antagonists for the treatment of metastatic lung cancer. Expert Rev Anticancer Ther. 2011 Apr;11(4):621-30. doi: 10.1586/era.11.11. Review. PubMed PMID: 21504328.
6: Beider K, Begin M, Abraham M, Wald H, Weiss ID, Wald O, Pikarsky E, Zeira E, Eizenberg O, Galun E, Hardan I, Engelhard D, Nagler A, Peled A. CXCR4 antagonist 4F-benzoyl-TN14003 inhibits leukemia and multiple myeloma tumor growth. Exp Hematol. 2011 Mar;39(3):282-92. doi: 10.1016/j.exphem.2010.11.010. Epub 2010 Dec 5. PubMed PMID: 21138752.
7: Burger JA, Stewart DJ. CXCR4 chemokine receptor antagonists: perspectives in SCLC. Expert Opin Investig Drugs. 2009 Apr;18(4):481-90. doi: 10.1517/13543780902804249 . Review. PubMed PMID: 19335276.
