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| 5mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
OTSSP167 HCl (OTS167 HCl), the hydrochloride salt of OTSSP-167 (OTS-167), is an orally bioavailable inhibitor of MELK (maternal embryonic leucine zipper kinase) with IC50 of 0.41 nM. OTSSP167 inhibits MELK-overexpressed cancer cells A549, T47D, DU4475, and 22Rv1 with IC50 values of 6.7, 4.3, 2.3, and 6.0 nM, respectively. OTSSP167 prevented the phosphorylation of two novel MELK substrates, PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which are crucial for stem cell properties and invasiveness. MELK is regarded as an appealing molecular target for cancer treatment because it is upregulated in a variety of human tumors. Thus, MELK inhibits apoptosis while promoting G2/M transition and EMT in GC, which in turn promotes cell growth and invasiveness. These findings imply that MELK may represent a promising target for GC therapy.
| Targets |
MELK (IC50 = 0.41 nM)
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| ln Vitro |
OTSSP167 inhibits the growth of A549 (lung), T47D (breast), DU4475 (breast), 22Rv1 (prostate) and HT1197 (bladder) cancer cells with IC50 values of 6.7, 4.3, 2.3, 6.0 and 97 nM, respectively[1].
OTSSP167 can abrogate the mitotic checkpoint, disrupt MCC and MCC-APC/C interaction in MCF7 cells. OTSSP167 causes GFP-MELK localization to cell cortex in prometaphase cells[2]. OTSSP167 is a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC50 of 0.41 nM[3]. |
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| ln Vivo |
OTSSP167 (20 mg/kg, i.v.) results in tumor growth inhibition (TGI) of 73% in xenograft mouse model; OTSSP167 (1, 5, and 10 mg/kg, p.o.) reveals TGI of 51, 91, and 108%, respectively. OTSSP167 (20 mg/kg, p.o.) shows no tumor growth suppressive effect on PC-14 xenografts[1].
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| Enzyme Assay |
MELK recombinant protein (0.4 μg) is mixed with 5 μg of each substrate in 20 μL of kinase buffer containing 30 mM Tris-HCl (pH), 10 mM DTT, 40 mM NaF, 10 mM MgCl2, 0.1 mM EGTA with 50 μM cold-ATP and 10 Ci of [γ-32P]ATP for 30 min at 30 °C. The reaction is terminated by addition of SDS sample buffer and boiled for 5 min prior to SDS-PAGE. The gel is dried and autoradiographed with intensifying screens at room temperature. OTSSP167 (final concentration of 10 nM) is dissolved in DMSO and added to kinase buffer before the incubation.
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| Cell Assay |
OTSSP167 inhibits cell proliferation of a variety of cancer cell lines including A549, T47D, DU4475 and 22Rv1. The IC50 values are 6.7nM, 4.3nM, 2.3nM and 6nM, respectively.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C25H29CL3N4O2
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|---|---|
| Molecular Weight |
523.88
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| Exact Mass |
522.135
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| Elemental Analysis |
C, 57.32; H, 5.58; Cl, 20.30; N, 10.69; O, 6.11
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| CAS # |
1431698-10-0
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| Related CAS # |
OTSSP167;1431697-89-0
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| PubChem CID |
135565272
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| Appearance |
Light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
648
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=C(C([H])=C(C=1[H])C1C([H])=C([H])C2C(=C(C(C(C([H])([H])[H])=O)=C([H])N=2)N([H])C2([H])C([H])([H])C([H])([H])C([H])(C([H])([H])N(C([H])([H])[H])C([H])([H])[H])C([H])([H])C2([H])[H])N=1)Cl)O[H].Cl[H]
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| InChi Key |
XDGWHISAOWEFML-BFLZMHAMSA-N
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| InChi Code |
InChI=1S/C25H28Cl2N4O2.ClH/c1-14(32)18-12-28-22-9-8-21(16-10-19(26)25(33)20(27)11-16)30-24(22)23(18)29-17-6-4-15(5-7-17)13-31(2)3;/h8-12,15,17,33H,4-7,13H2,1-3H3,(H,28,29);1H/t15-,17-;
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| Chemical Name |
1-(6-(3,5-dichloro-4-hydroxyphenyl)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)ethanone hydrochloride
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| Synonyms |
OTSSP167; OTSSP-167; OTS-167; OTS 167; OTSSP 167; OTS167; OTS167 HCl; OTSSP167 hydrochlorideOTSSP167 HCl
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (5.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (5.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 3 mg/mL (5.73 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 1 mg/mL (1.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9088 mL | 9.5442 mL | 19.0883 mL | |
| 5 mM | 0.3818 mL | 1.9088 mL | 3.8177 mL | |
| 10 mM | 0.1909 mL | 0.9544 mL | 1.9088 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 | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02926690 | Recruiting | Drug: OTS167PO | Relapsed/Refractory Locally Advanced | OncoTherapy Science, Inc. | May 29, 2017 | Phase 1 |
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