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Purity: ≥98%
DTP3 (DTP-3) is a novel, potent and selective inhibitor of GADD45β/MKK7 ((growth arrest and DNA-damage-inducible β/mitogen-activated protein kinase kinase 7) with potential anticancer activity. It blocks the NF-κB survival pathway specifically in cancer. In a mouse plasmacytoma model, DTP3 demonstrates strong antitumor activity against MM. DTP3 dissociated the GADD45b/MKK7 complex through an allosteric mechanism after binding to MKK7, causing the kinase to rearrange its conformation. DTP3 was completely inactive in tumor cell lines with low GADD45B expression, but it inhibited cell growth and showed potent and selective activity in both MM and non-MM cell lines with high GADD45B expression.
| Targets |
GADD45β/MKK7; NF-κB
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|---|---|
| ln Vitro |
DTP3 physically interacts with MKK7, both in isolation and within the complex with GADD45β, and dissociates the GADD45β/MKK7 complex via an allosteric mechanism. Without being toxic to healthy cells, DTP3 selectively kills cells and triggers apoptosis in MM cells with functional MKK7 and increased GADD45β expression. Additionally, DTP3 exhibits synergistic activity with bortezomib in two different MM cell lines, showing a combination index of 0.21 in U266 cells and of 0.56 in KMS-12 cells. [1]
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| ln Vivo |
DTP3 (14.5 mg/kg/day) displays strong antitumor activity against MM in mouse plasmacytoma model. [1]
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| Enzyme Assay |
Tryptophan fluorescence quenching analysis, used after a nonlinear regression algorithm has been used to fit the fluorescence data, is used to determine the stoichiometry and KD value of the DTP3/MKK7 interaction.
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| Cell Assay |
[3H]Assays for thymidine incorporation are carried out according to established protocols. Briefly, cell lines are seeded into 96-well plates at 1.0x104 cells per well and either left untreated or treated daily with the indicated concentrations of peptides. They are then maintained in complete RPMI-1640 medium at 37°C in 5% CO2, splitting them with medium as necessary. Cells are incubated for an additional 16 hours with 0.037 MBq/well of [3H]thymidine at 24, 72, or 144 hours. Following this, they are harvested onto glass fiber filter mats using a 96-well plate automated Tomtec cell harvester, and their liquid scintillation spectroscopy data is analyzed using a LKB Wallac Trilux Microbeta 3-counter. Values are expressed as the proportion of counts per minute (cpm) measured in the treated cultures to the corresponding untreated cultures. The mean compound concentration causing a 50% inhibition of [3H]thymidine uptake as compared to the uptake measured in untreated cells is known as the IC50 value, which is calculated using either 5 or 7 concentrations of the compound. Trypan blue exclusion assays are performed. Briefly, 2.0x105 cells from lentivirus-infected cell lines are seeded into the wells of 48-well plates in complete medium, and they are then cultured at 37°C in 5% CO2, splitting them as necessary during the assays. Trypan blue is used to count cells, and cell viability is monitored over a period of up to 8 days. The numbers of live infected cells in the cultures are extrapolated, as needed, from the cell counts by taking into account the percentages of eGFP+ cells, using flow cytometry. The percentage of live infected cells present in the cultures at the indicated times compared to the number of live infected cells present in the same cultures on day 0 is used to express values.
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| Animal Protocol |
NOD/SCID mice bearing U266 or KMS-11 MM cells
14.5 mg/kg/day Administered using Alzet osmotic pumps |
| References |
| Molecular Formula |
C26H35N7O5
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|---|---|---|
| Molecular Weight |
525.6
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| Exact Mass |
525.27
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| Elemental Analysis |
C, 59.41; H, 6.71; N, 18.65; O, 15.22
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| CAS # |
1809784-29-9
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| Related CAS # |
DTP3 TFA;2759216-46-9
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| Appearance |
Solid powder
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| SMILES |
CC(=O)N[C@H](CC1=CC=C(C=C1)O)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CC2=CC=CC=C2)C(=O)N
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| InChi Key |
AOUZPXZGMZUQQS-YPAWHYETSA-N
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| InChi Code |
InChI=1S/C26H35N7O5/c1-16(34)31-22(15-18-9-11-19(35)12-10-18)25(38)32-20(8-5-13-30-26(28)29)24(37)33-21(23(27)36)14-17-6-3-2-4-7-17/h2-4,6-7,9-12,20-22,35H,5,8,13-15H2,1H3,(H2,27,36)(H,31,34)(H,32,38)(H,33,37)(H4,28,29,30)/t20-,21-,22-/m1/s1
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| Chemical Name |
(2R)-2-[[(2R)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-N-[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9026 mL | 9.5129 mL | 19.0259 mL | |
| 5 mM | 0.3805 mL | 1.9026 mL | 3.8052 mL | |
| 10 mM | 0.1903 mL | 0.9513 mL | 1.9026 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00244673 | Completed | Biological: DTP3/4+OPV+MV versus OPV+MV or DTP4+OPV4 versus OPV4 |
Mortality Hospitalization |
Bandim Health Project | October 2005 | Phase 4 |
The High Target Specificity of DTP3 in Cells. Cancer Cell. 2014 Oct 13; 26(4): 495–508. |
Products are for research use only; We do not sell to patients 
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COA
