Synonym
ProTAME; pro-Tosyl-L-Arginine Methyl Ester;
IUPAC/Chemical Name
(S,E)-5-((5-methoxy-4-((4-methylphenyl)sulfonamido)-5-oxopentyl)amino)-3,7-dioxo-2,8-dioxa-4,6-diazanon-4-ene-1,9-diyl bis(2-phenylacetate)
InChi Key
MHYOVHULCQSDRZ-NDEPHWFRSA-N
InChi Code
InChI=1S/C34H38N4O12S/c1-24-15-17-27(18-16-24)51(44,45)38-28(31(41)46-2)14-9-19-35-32(36-33(42)49-22-47-29(39)20-25-10-5-3-6-11-25)37-34(43)50-23-48-30(40)21-26-12-7-4-8-13-26/h3-8,10-13,15-18,28,38H,9,14,19-23H2,1-2H3,(H2,35,36,37,42,43)/t28-/m0/s1
SMILES Code
O=C(OCOC(/N=C(NCCC[C@H](NS(C1=CC=C(C)C=C1)(=O)=O)C(OC)=O)/NC(OCOC(CC2=CC=CC=C2)=O)=O)=O)CC3=CC=CC=C3
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
Biological target:
ProTAME is a small-molecule inhibitor of APC/C, with chemotherapeutic drugs efficiently targets osteosarcoma in vitro. ProTAME
strongly enhanced the anti-lymphoma effect of clinically relevant agents, doxorubicin and venetoclax. Combining proTAME with
another APC/C inhibitor apcin or the alkylating agent melphalan resulted in enhanced anti-MM activity.
In vitro activity:
. ProTAME prevented the mitotic exit of PTX-treated cells, prolonged mitosis, and induced apoptosis, demonstrating its
effectiveness in enhancing PTX cytotoxicity. The data suggested that forced mitotic exit, facilitated by proTAME, might be a
more successful anticancer strategy than blocking mitotic exit by inactivation of the APC/C.
Reference: Cell Cycle. 2013 Aug 15;12(16):2598-607
In vivo activity:
To Be Determined
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
36.3 |
50.00 |
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
726.75
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:
Giovinazzi S, Bellapu D, Morozov VM, Ishov AM. Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy. Cell Cycle. 2013 Aug 15;12(16):2598-607. doi: 10.4161/cc.25591. Epub 2013 Jul 9. PMID: 23907120; PMCID: PMC3865049.
Crawford LJ, Anderson G, Johnston CK, Irvine AE. Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma. Oncotarget. 2016 Oct 25;7(43):70481-70493. doi: 10.18632/oncotarget.12026. PMID: 27655696; PMCID: PMC5342567.
In vitro protocol:
Giovinazzi S, Bellapu D, Morozov VM, Ishov AM. Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy. Cell Cycle. 2013 Aug 15;12(16):2598-607. doi: 10.4161/cc.25591. Epub 2013 Jul 9. PMID: 23907120; PMCID: PMC3865049.
Crawford LJ, Anderson G, Johnston CK, Irvine AE. Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma. Oncotarget. 2016 Oct 25;7(43):70481-70493. doi: 10.18632/oncotarget.12026. PMID: 27655696; PMCID: PMC5342567.
In vivo protocol:
To Be Determined
1: Crawford LJ, Anderson G, Johnston CK, Irvine AE. Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma. Oncotarget. 2016 Oct 25;7(43):70481-70493. doi: 10.18632/oncotarget.12026. PubMed PMID: 27655696; PubMed Central PMCID: PMC5342567.
2: Lub S, Maes A, Maes K, De Veirman K, De Bruyne E, Menu E, Fostier K, Kassambara A, Moreaux J, Hose D, Leleu X, King RW, Vanderkerken K, Van Valckenborgh E. Inhibiting the anaphase promoting complex/cyclosome induces a metaphase arrest and cell death in multiple myeloma cells. Oncotarget. 2016 Jan 26;7(4):4062-76. doi: 10.18632/oncotarget.6768. PubMed PMID: 26716651; PubMed Central PMCID: PMC4826190.
3: Giovinazzi S, Bellapu D, Morozov VM, Ishov AM. Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy. Cell Cycle. 2013 Aug 15;12(16):2598-607. doi: 10.4161/cc.25591. Epub 2013 Jul 9. PubMed PMID: 23907120; PubMed Central PMCID: PMC3865049.
4: Hu K, Liao D, Wu W, Han AJ, Shi HJ, Wang F, Wang X, Zhong L, Duan T, Wu Y, Cao J, Tang J, Sang Y, Wang L, Lv X, Xu S, Zhang RH, Deng WG, Li SP, Zeng YX, Kang T. Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma. Oncotarget. 2014 May 30;5(10):3088-100. PubMed PMID: 24840027; PubMed Central PMCID: PMC4102794.
5: Lara-Gonzalez P, Taylor SS. Cohesion fatigue explains why pharmacological inhibition of the APC/C induces a spindle checkpoint-dependent mitotic arrest. PLoS One. 2012;7(11):e49041. doi: 10.1371/journal.pone.0049041. Epub 2012 Nov 7. PubMed PMID: 23145059; PubMed Central PMCID: PMC3492190.
