Synonym
BIO-5192; BIO5192; BIO 5192; AMD-15057; AMD 15057; AMD15057;
IUPAC/Chemical Name
Butanoic acid, 1-((3,5-dichlorophenyl)sulfonyl)-L-prolyl-N4-(N-methyl-N-((4-((((2-methylphenyl)amino)carbonyl)amino)phenyl)acetyl)-L-leucyl)-2,4-diamino-, (2S)-
InChi Key
MNQBPRHHZPXCKZ-ZDCRTTOTSA-N
InChi Code
1S/C38H46Cl2N6O8S/c1-23(2)18-33(45(4)34(47)19-25-11-13-28(14-12-25)42-38(52)44-30-9-6-5-8-24(30)3)35(48)41-16-15-31(37(50)51)43-36(49)32-10-7-17-46(32)55(53,54)29-21-26(39)20-27(40)22-29/h5-6,8-9,11-14,20-23,31-33H,7,10,15-19H2,1-4H3,(H,41,48)(H,43,49)(H,50,51)(H2,42,44,52)/t31-,32-,33-/m0/s1
SMILES Code
O=C(O)[C@@H](NC([C@H]1N(S(=O)(C2=CC(Cl)=CC(Cl)=C2)=O)CCC1)=O)CCNC([C@H](CC(C)C)N(C)C(CC3=CC=C(NC(NC4=CC=CC=C4C)=O)C=C3)=O)=O
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
Shelf Life
>3 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
2934.99.03.00
Biological target:
BIO5192 is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd<10 pM).
In vitro activity:
BIO5192 is a selective and potent small molecule inhibitor of VLA-4, with an affinity of 250- to 1000-fold higher than for the related α4β7 integrin. BIO5192 reduced both untreated and phorbol 12-myristate 13-acetate–stimulated cell binding to fibronectin-coated plates by 43% and 36%, respectively, indicating that BIO5192 blocks binding to multiple activation states of VLA-4 (Figure 1A; P < .001).
Reference: Blood. 2009 Aug 13; 114(7): 1340–1343. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727418/
In vivo activity:
First, rats were treated intravenously with BIO5192 (10 mg/kg) or with vehicle (controls) to assess effects of integrin blockade for 24 h or 72 h after thoracic clip-compression SCI. BIO5192 treatment significantly decreased the MPO enzymatic activity (neutrophil infiltration) and ED-1 expression (macrophage density) by 40% and 38% at 24 h and by 52% and 25% at 72 h post injury, respectively. In cord homogenates, BIO5192 treatment decreased expression of the oxidative enzymes gp91(phox), inducible nitric oxide and cyclooxygenase-2 by approximately 40% at both times of analysis.
Reference: Exp Neurol. 2008 Dec;214(2):160-7. https://pubmed.ncbi.nlm.nih.gov/18926823/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
81.8 |
100.00 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
817.78
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. Ramirez P, Rettig MP, Uy GL, Deych E, Holt MS, Ritchey JK, DiPersio JF. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009 Aug 13;114(7):1340-3. doi: 10.1182/blood-2008-10-184721. Epub 2009 Jul 1. PMID: 19571319; PMCID: PMC2727418.
2. Bao F, Chen Y, Schneider KA, Weaver LC. An integrin inhibiting molecule decreases oxidative damage and improves neurological function after spinal cord injury. Exp Neurol. 2008 Dec;214(2):160-7. doi: 10.1016/j.expneurol.2008.09.006. Epub 2008 Sep 26. PMID: 18926823.
In vitro protocol:
1. Ramirez P, Rettig MP, Uy GL, Deych E, Holt MS, Ritchey JK, DiPersio JF. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009 Aug 13;114(7):1340-3. doi: 10.1182/blood-2008-10-184721. Epub 2009 Jul 1. PMID: 19571319; PMCID: PMC2727418.
In vivo protocol:
1. Bao F, Chen Y, Schneider KA, Weaver LC. An integrin inhibiting molecule decreases oxidative damage and improves neurological function after spinal cord injury. Exp Neurol. 2008 Dec;214(2):160-7. doi: 10.1016/j.expneurol.2008.09.006. Epub 2008 Sep 26. PMID: 18926823.
1: Ramirez P, Rettig MP, Uy GL, Deych E, Holt MS, Ritchey JK, DiPersio JF. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009 Aug 13;114(7):1340-3. doi: 10.1182/blood-2008-10-184721. Epub 2009 Jul 1. PubMed PMID: 19571319; PubMed Central PMCID: PMC2727418.
2: Leone DR, Giza K, Gill A, Dolinski BM, Yang W, Perper S, Scott DM, Lee WC, Cornebise M, Wortham K, Nickerson-Nutter C, Chen LL, LePage D, Spell JC, Whalley ET, Petter RC, Adams SP, Lobb RR, Pepinsky RB. An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther. 2003 Jun;305(3):1150-62. Epub 2003 Mar 6. PubMed PMID: 12626659.
