AZD1208 hydrochloride is a novel, potent, highly selective and orally bioavailable small molecule pan-inhibitor of Pim kinase with IC50 of 0.4 nM, 5 nM, and 1.9 nM for Pim1, Pim2, and Pim3 in cell-free assays, respectively. As a Pan-PIM kinase inhibitor, AZD1208 demonstrated a broad spectrum of antineoplastic activity against various cancers such as breast, prostate, AML, and non-Hodgkin lymphomas. The mechanism of action of AZD1208 is to inhibit the activities of PIM1/2/3 serine/threonine kinases, which may result in the interruption of the G1/S phase of cell cycle transition, therefore causing cell cycle arrest and inducing apoptosis in cells that overexpress PIMs.
Physicochemical Properties
| Molecular Formula | C21H22CLN3O2S | |
| Molecular Weight | 415.936282634735 | |
| Exact Mass | 415.112 | |
| CAS # | 1621866-96-3 | |
| Related CAS # | AZD1208;1204144-28-4 | |
| PubChem CID | 76962885 | |
| Appearance | Typically exists as solid at room temperature | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 5 | |
| Rotatable Bond Count | 3 | |
| Heavy Atom Count | 28 | |
| Complexity | 602 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | C1C[C@H](CN(C1)C2=C(C=CC=C2C3=CC=CC=C3)/C=C\4/C(=O)NC(=O)S4)N.Cl |
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| InChi Key | KPQHIFXAXSIKOA-SLWUYDEESA-N | |
| InChi Code | InChI=1S/C21H21N3O2S.ClH/c22-16-9-5-11-24(13-16)19-15(12-18-20(25)23-21(26)27-18)8-4-10-17(19)14-6-2-1-3-7-14;/h1-4,6-8,10,12,16H,5,9,11,13,22H2,(H,23,25,26);1H/b18-12-;/t16-;/m1./s1 | |
| Chemical Name | (5Z)-5-[[2-[(3R)-3-aminopiperidin-1-yl]-3-phenylphenyl]methylidene]-1,3-thiazolidine-2,4-dione;hydrochloride | |
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| HS Tariff Code | 2934.99.9001 | |
| 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) |
Biological Activity
| ln Vitro | With GI50 values less than 100 nM, AZD1208 hydrochloride has strong antiproliferative action in the megakaryoblastic leukemia cell line MOLM-16[1]. The proliferation of Ramos cells is inhibited by AZD1208 hydrochloride (10 μM), and at 1 μM, it substantially inhibits PIM kinases in all cells. Apoptosis is induced by AZD1208 hydrochloride, and PIM2 knockdown mostly results in a change in the cell cycle[2]. When combined, AZD1208 hydrochloride and AZD2014 significantly block AKT and 4EBP1 activation, reduce polysome formation, and quickly activate AMPKα, a negative regulator of translation machinery through mTORC1/2 signaling in AML cells[3]. | ||
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| Animal Protocol |
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| References |
[1]. Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4599-604. [2]. Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas. Mol Cancer. 2015 Dec 8;14:205. [3]. The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression. Oncotarget. 2015 Nov 10;6(35):37930-47. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4042 mL | 12.0210 mL | 24.0419 mL | |
| 5 mM | 0.4808 mL | 2.4042 mL | 4.8084 mL | |
| 10 mM | 0.2404 mL | 1.2021 mL | 2.4042 mL |