AZD1208PIM kinase inhibitor CAS# 1204144-28-4 |
2D Structure
- Ro 31-8220 Mesylate
Catalog No.:BCC4999
CAS No.:138489-18-6
- CHIR-99021 (CT99021)
Catalog No.:BCC1275
CAS No.:252917-06-9
- CHIR-98014
Catalog No.:BCC3751
CAS No.:252935-94-7
- TWS119
Catalog No.:BCC4512
CAS No.:601514-19-6
- GSK-3 inhibitor 1
Catalog No.:BCC4126
CAS No.:603272-51-1
- GSK-3 Inhibitor IX (BIO)
Catalog No.:BCC4510
CAS No.:667463-62-9
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
Cas No. | 1204144-28-4 | SDF | Download SDF |
PubChem ID | 58423153 | Appearance | Powder |
Formula | C21H21N3O2S | M.Wt | 379.48 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 50 mg/mL (131.76 mM; Need ultrasonic) | ||
Chemical Name | (5Z)-5-[[2-[(3R)-3-aminopiperidin-1-yl]-3-phenylphenyl]methylidene]-1,3-thiazolidine-2,4-dione | ||
SMILES | C1CC(CN(C1)C2=C(C=CC=C2C=C3C(=O)NC(=O)S3)C4=CC=CC=C4)N | ||
Standard InChIKey | MCUJKPPARUPFJM-UWCCDQBKSA-N | ||
Standard InChI | InChI=1S/C21H21N3O2S/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)/b18-12-/t16-/m1/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | AZD1208 is a potent, and orally available inhibitor of Pim kinase with IC50 values of 0.4 nM, 5 nM, and 1.9 nM for Pim1, Pim2, and Pim3, respectively. | |||||
Targets | Pim1 | Pim2 | Pim3 | |||
IC50 | 0.4 nM | 1.9 nM | 5 nM |
AZD1208 Dilution Calculator
AZD1208 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.6352 mL | 13.1759 mL | 26.3518 mL | 52.7037 mL | 65.8796 mL |
5 mM | 0.527 mL | 2.6352 mL | 5.2704 mL | 10.5407 mL | 13.1759 mL |
10 mM | 0.2635 mL | 1.3176 mL | 2.6352 mL | 5.2704 mL | 6.588 mL |
50 mM | 0.0527 mL | 0.2635 mL | 0.527 mL | 1.0541 mL | 1.3176 mL |
100 mM | 0.0264 mL | 0.1318 mL | 0.2635 mL | 0.527 mL | 0.6588 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
IC50: 0.4 nM for Pim-1, 5.0 nM for Pim-2, and 1.9 nM for Pim-3
Upregulation of Pim kinases has been observed in several types of leukemias and lymphomas. Pim-1, -2, and -3 promote cell proliferation and survival downstream of cytokine and growth factor signaling pathways. AZD1208 is a potent, highly selective, and orally available Pim kinase inhibitor.
In vitro: AZD1208 inhibited the growth of 5 of 14 acute myeloid leukemia (AML) cell lines tested. In MOLM-16 cells, AZD1208 also causes cell cycle arrest and apoptosis, accompanied by a dose-dependent reduction in phosphorylation of Bcl-2 antagonist of cell death [1].
In vivo: AZD1208 inhibits the growth of KG-1a and MOLM-16 xenograft tumors in vivo with a clear PK/PD relationship. Treatment with 10 mg/kg or 30 mg/kg of AZD1208 led to an 89% tumor growth inhibition or slight regression, respectively [1].
Clinical trials: AZD1208 is in Phase I trials evaluating the safety and tolerability profile and to determine the maximum tolerated dose (MTD). There are two ongoing trials where AZD1208 has been orally administered in AML and solid tumor (of all types) patients
Reference:
[1] Keeton EK, McEachern K, Dillman KS, Palakurthi S, Cao Y, Grondine MR, Kaur S, Wang S, Chen Y, Wu A, Shen M, Gibbons FD, Lamb ML, Zheng X, Stone RM, Deangelo DJ, Platanias LC, Dakin LA, Chen H, Lyne PD, Huszar D. AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia. Blood. 2014;123(6):905-13.
- Biapenem
Catalog No.:BCC1071
CAS No.:120410-24-4
- Jionoside B1
Catalog No.:BCN2858
CAS No.:120406-37-3
- AS 1949490
Catalog No.:BCC7762
CAS No.:1203680-76-5
- Cyclotraxin B
Catalog No.:BCC6357
CAS No.:1203586-72-4
- DASA-58
Catalog No.:BCC6522
CAS No.:1203494-49-8
- Citroside A
Catalog No.:BCN7294
CAS No.:120330-44-1
- CX-6258
Catalog No.:BCC1504
CAS No.:1202916-90-2
- Dorzolamide
Catalog No.:BCC4287
CAS No.:120279-96-1
- 4-Hydroxysapriparaquinone
Catalog No.:BCN4806
CAS No.:120278-25-3
- Salvinolone
Catalog No.:BCN3215
CAS No.:120278-22-0
- CNX-774
Catalog No.:BCC4394
CAS No.:1202759-32-7
- AVL-292
Catalog No.:BCC1385
CAS No.:1202757-89-8
- Icotinib Hydrochloride
Catalog No.:BCC1639
CAS No.:1204313-51-8
- TMC647055
Catalog No.:BCC6376
CAS No.:1204416-97-6
- Verlukast
Catalog No.:BCC2035
CAS No.:120443-16-5
- Jionoside A1
Catalog No.:BCN2922
CAS No.:120444-60-2
- (±)-Vesamicol hydrochloride
Catalog No.:BCC6737
CAS No.:120447-62-3
- ER 27319 maleate
Catalog No.:BCC5914
CAS No.:1204480-26-1
- Lophanthoidin B
Catalog No.:BCN6091
CAS No.:120462-42-2
- Lophanthoidin E
Catalog No.:BCN6092
CAS No.:120462-45-5
- Lophanthoidin F
Catalog No.:BCN6093
CAS No.:120462-46-6
- Ganoderenic acid F
Catalog No.:BCN2446
CAS No.:120462-47-7
- Ganoderenic acid H
Catalog No.:BCN2447
CAS No.:120462-48-8
- Pinanediol talabostat boronate
Catalog No.:BCC1640
CAS No.:1204669-37-3
Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas.[Pubmed:26643319]
Mol Cancer. 2015 Dec 8;14:205.
BACKGROUND: A promising therapeutic approach for aggressive B-cell Non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) is to target kinases involved in signal transduction and gene regulation. PIM1/2 serine/threonine kinases are highly expressed in activated B-cell-like DLBCL (ABC-DLBCL) with poor prognosis. In addition, both PIM kinases have a reported synergistic effect with c-MYC in mediating tumour development in several cancers, c-MYC gene being translocated to one of the immunoglobulin loci in nearly all BLs. METHODS: For these reasons, we tested the efficiency of several PIM kinase inhibitors (AZD1208, SMI4a, PIM1/2 inhibitor VI and Quercetagetin) in preventing proliferation of aggressive NHL-derived cell lines and compared their efficiency with PIM1 and/or PIM2 knockdown. RESULTS: We observed that most of the anti-proliferative potential of these inhibitors in NHL was due to an off-target effect. Interestingly, we present evidence of a kinase-independent function of PIM2 in regulating cell cycle. Moreover, combining AZD1208 treatment and PIM2 knockdown additively repressed cell proliferation. CONCLUSION: Taken together, this study suggests that at least a part of PIM1/2 oncogenic potential could be independent of their kinase activity, justifying the limited anti-tumorigenic outcome of PIM-kinase inhibitors in NHL.
Protein profiling identifies mTOR pathway modulation and cytostatic effects of Pim kinase inhibitor, AZD1208, in acute myeloid leukemia.[Pubmed:27054578]
Leuk Lymphoma. 2016 Dec;57(12):2863-2873.
Pim kinases phosphorylate and regulate a number of key acute myeloid leukemia (AML) cell survival proteins, and Pim inhibitors have recently entered clinical trial for hematological malignancies. AZD1208 is a small molecule pan-Pim kinase inhibitor and AZD1208 treatment resulted in growth inhibition and cell size reduction in AML cell lines including FLT3-WT (OCI-AML-3, KG-1a, and MOLM-16) and FLT3-ITD mutated (MOLM-13 and MV-4-11). There was limited apoptosis induction (<10% increase) in the AML cell lines evaluated with up to 3 muM AZD1208 for 24 h, suggesting that growth inhibition is not through apoptosis induction. Using reverse phase protein array (RPPA) and immunoblot analysis, we identified that AZD1208 resulted in suppression of mTOR signaling, including inhibition of protein phosphorylation of mTOR (Ser2448), p70S6K (Thr389), S6 (Ser235/236), and 4E-BP1 (Ser65). Consistent with mTOR inhibition, there was also a reduction in protein synthesis that correlated with cell size reduction and growth inhibition with AZD1208; our study provides insights into the mechanism of AZD1208.
The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression.[Pubmed:26473447]
Oncotarget. 2015 Nov 10;6(35):37930-47.
Mammalian target of rapamycin (mTOR) signaling is a critical pathway in the biology of acute myeloid leukemia (AML). Proviral integration site for moloney murine leukemia virus (PIM) serine/threonine kinase signaling takes part in various pathways exerting tumorigenic properties. We hypothesized that the combination of a PIM kinase inhibitor with an mTOR inhibitor might have complementary growth-inhibitory effects against AML. The simultaneous inhibition of the PIM kinase by pan-PIM inhibitor AZD1208 and of mTOR by selective mTORC1/2 dual inhibitor AZD2014 exerted anticancer properties in AML cell lines and in cells derived from primary AML samples with or without supportive stromal cell co-culture, leading to suppressed proliferation and increased apoptosis. The combination of AZD1208 and AZD2014 rapidly activated AMPKalpha, a negative regulator of translation machinery through mTORC1/2 signaling in AML cells; profoundly inhibited AKT and 4EBP1 activation; and suppressed polysome formation. Inhibition of both mTOR and PIM counteracted induction of heat-shock family proteins, uncovering the master negative regulation of heat shock factor 1 (HSF1), the dominant transcription factor controlling cellular stress responses. The novel combination of the dual mTOR inhibitor and pan-PIM inhibitor synergistically inhibited AML growth by effectively reducing protein synthesis through heat shock factor pathway suppression.