Synonym
EOAI 402143; EOAI 3402143; EOAI-3402143; EOAI3402143; G9 free base; G9 free base
IUPAC/Chemical Name
2-Cyano-3-(3,6-dichloro-pyridin-2-yl)-N-{1-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-butyl}-acrylamide
InChi Key
IIKVQQNZHGBYGQ-KNTRCKAVSA-N
InChi Code
InChI=1S/C25H28Cl2N4O3/c1-2-3-22(30-25(32)19(17-28)16-23-21(26)8-9-24(27)29-23)18-4-6-20(7-5-18)34-15-12-31-10-13-33-14-11-31/h4-9,16,22H,2-3,10-15H2,1H3,(H,30,32)/b19-16+
SMILES Code
O=C(NC(C1=CC=C(OCCN2CCOCC2)C=C1)CCC)/C(C#N)=C/C3=NC(Cl)=CC=C3Cl
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
>2 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
Usp9x was recently shown to be highly expressed in myeloma patients with short progression-free survival and is proposed to enhance stability of the survival protein Mcl-1
Biological target:
EOAI3402143 is a deubiquitinase (DUB) inhibitor, which inhibits dose-dependently inhibits Usp9x/Usp24 and Usp5.
In vitro activity:
In A375R cells, G9 (EOAI3402143) reduced pERK, pStat3 and elevated NOXA levels, the latter related to Usp9x inhibition by G9 (Fig. 6E).
Reference: Oncotarget. 2014 Jul; 5(14): 5559–5569. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170643/
In vivo activity:
Animals with subcutaneous MM1.S tumors were treated with G9 (EOAI3402143) doses ranging from 2.5 to 10 mg/kg intraperitoneally once per day for 2 weeks. As shown in Figure 7A, G9 doses at or above 5 mg/kg significantly suppressed tumor growth, noted as early as 3 days after initiating dosing. Animal weight was not adversely affected throughout the treatment interval (Figure 7B). Tumor regrowth was observed after discontinuation of G9 dosing (supplemental Figure 5A), which demonstrated a dose-dependent delay in resumption of tumor growth after stopping G9 treatment.
Reference: Blood. 2015 Jun 4;125(23):3588-97. https://pubmed.ncbi.nlm.nih.gov/25814533/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
75.0 |
148.98 |
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
503.42
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. Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young M, Showalter HD, Sun D, Jakubowiak A, Malek SN, Talpaz M, Donato NJ. Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood. 2015 Jun 4;125(23):3588-97. doi: 10.1182/blood-2014-10-605584. Epub 2015 Mar 26. PMID: 25814533.
2. Potu H, Peterson LF, Pal A, Verhaegen M, Cao J, Talpaz M, Donato NJ. Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway. Oncotarget. 2014 Jul 30;5(14):5559-69. doi: 10.18632/oncotarget.2140. PMID: 24980819; PMCID: PMC4170643.
In vitro protocol:
1. Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young M, Showalter HD, Sun D, Jakubowiak A, Malek SN, Talpaz M, Donato NJ. Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood. 2015 Jun 4;125(23):3588-97. doi: 10.1182/blood-2014-10-605584. Epub 2015 Mar 26. PMID: 25814533.
2. Potu H, Peterson LF, Pal A, Verhaegen M, Cao J, Talpaz M, Donato NJ. Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway. Oncotarget. 2014 Jul 30;5(14):5559-69. doi: 10.18632/oncotarget.2140. PMID: 24980819; PMCID: PMC4170643.
In vivo protocol:
1. Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young M, Showalter HD, Sun D, Jakubowiak A, Malek SN, Talpaz M, Donato NJ. Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood. 2015 Jun 4;125(23):3588-97. doi: 10.1182/blood-2014-10-605584. Epub 2015 Mar 26. PMID: 25814533.
1: Akiyama H, Umezawa Y, Watanabe D, Okada K, Ishida S, Nogami A, Miura O. Inhibition of USP9X Downregulates JAK2-V617F and Induces Apoptosis Synergistically with BH3 Mimetics Preferentially in Ruxolitinib-Persistent JAK2-V617F-Positive Leukemic Cells. Cancers (Basel). 2020 Feb 10;12(2):406. doi: 10.3390/cancers12020406. PMID: 32050632; PMCID: PMC7072561.
2: Akiyama H, Umezawa Y, Ishida S, Okada K, Nogami A, Miura O. Inhibition of USP9X induces apoptosis in FLT3-ITD-positive AML cells cooperatively by inhibiting the mutant kinase through aggresomal translocation and inducing oxidative stress. Cancer Lett. 2019 Jul 1;453:84-94. doi: 10.1016/j.canlet.2019.03.046. Epub 2019 Apr 1. PMID: 30946869.
3: Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young M, Showalter HD, Sun D, Jakubowiak A, Malek SN, Talpaz M, Donato NJ. Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood. 2015 Jun 4;125(23):3588-97. doi: 10.1182/blood-2014-10-605584. Epub 2015 Mar 26. PMID: 25814533.
4: Potu H, Peterson LF, Pal A, Verhaegen M, Cao J, Talpaz M, Donato NJ. Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway. Oncotarget. 2014 Jul 30;5(14):5559-69. doi: 10.18632/oncotarget.2140. PMID: 24980819; PMCID: PMC4170643.
