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MedKoo Cat#: 593164 | Name: GMB475
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

GMB-475 is a degrader of BCR-ABL1 tyrosine kinase based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 targets BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein. GMB-475 reduced viability and increased apoptosis in primary CML CD34+ cells, with no effect on healthy CD34+ cells at identical concentrations.

Chemical Structure

GMB475
GMB475
CAS#2490599-18-1

Theoretical Analysis

MedKoo Cat#: 593164

Name: GMB475

CAS#: 2490599-18-1

Chemical Formula: C43H46F3N7O7S

Exact Mass: 861.3132

Molecular Weight: 861.94

Elemental Analysis: C, 59.92; H, 5.38; F, 6.61; N, 11.38; O, 12.99; S, 3.72

Price and Availability

Size Price Availability Quantity
25mg USD 450.00 2 Weeks
50mg USD 750.00 2 Weeks
100mg USD 1,250.00 2 Weeks
200mg USD 2,050.00 2 Weeks
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Related CAS #
No Data
Synonym
GMB475; GMB 475; GMB-475;
IUPAC/Chemical Name
(2S)-1-((R)-3,3-dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
InChi Key
ONDVWISBMHHLGZ-CQQKSQRMSA-N
InChi Code
InChI=1S/C43H46F3N7O7S/c1-26-38(61-25-50-26)29-7-5-27(6-8-29)21-47-40(56)35-19-31(54)22-53(35)41(57)39(42(2,3)4)52-37(55)23-58-17-18-59-32-13-9-28(10-14-32)34-20-36(49-24-48-34)51-30-11-15-33(16-12-30)60-43(44,45)46/h5-16,20,24-25,31,35,39,54H,17-19,21-23H2,1-4H3,(H,47,56)(H,52,55)(H,48,49,51)/t31?,35-,39-/m0/s1
SMILES Code
FC(F)(F)OC1=CC=C(NC2=CC(C3=CC=C(OCCOCC(N[C@H](C(C)(C)C)C(N4[C@H](C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)CC(O)C4)=O)=O)C=C3)=NC=N2)C=C1
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
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
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
GMB-475 is a degrader of BCR-ABL1 tyrosine kinase based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 targets BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein.
In vitro activity:
GMB-475 induced the degradation of BCR-ABL1 and c-ABL1 in the context of both K562 (Fig. 2A) and Ba/F3 (Fig. 2B) cells with concomitant inhibition of downstream signaling via the STAT5 pathway, in a dose- and time-dependent fashion (human and murine VHL share >70% identity). In both cases, GMB-475 was capable of inhibiting cell proliferation with an IC50 of approximately 1 μM (Fig. 2C//D).D). Reference: Cancer Res. 2019 Sep 15;79(18):4744-4753. https://pubmed.ncbi.nlm.nih.gov/31311809/
In vivo activity:
TBD
Solvent mg/mL mM
Solubility
DMSO 145.4 168.69
Ethanol 50.0 58.01
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 861.94 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.

Recalculate based on batch purity %
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. Burslem GM, Schultz AR, Bondeson DP, Eide CA, Savage Stevens SL, Druker BJ, Crews CM. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019 Sep 15;79(18):4744-4753. doi: 10.1158/0008-5472.CAN-19-1236. Epub 2019 Jul 16. PMID: 31311809; PMCID: PMC6893872.
In vitro protocol:
1. Burslem GM, Schultz AR, Bondeson DP, Eide CA, Savage Stevens SL, Druker BJ, Crews CM. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019 Sep 15;79(18):4744-4753. doi: 10.1158/0008-5472.CAN-19-1236. Epub 2019 Jul 16. PMID: 31311809; PMCID: PMC6893872.
In vivo protocol:
TBD
1: Burslem GM, Schultz AR, Bondeson DP, Eide CA, Savage Stevens SL, Druker BJ, Crews CM. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019 Sep 15;79(18):4744-4753. doi: 10.1158/0008-5472.CAN-19-1236. Epub 2019 Jul 16. PubMed PMID: 31311809; PubMed Central PMCID: PMC6893872.