WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526614
CAS#: 1354825-58-3
Description: WEHI-345 is a potent and selective RIPK2 inhibitor which shows NOD signalling events yet prevents inflammatory cytokine production. WEHI-345 delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement. Despite only delaying NF-κB activation on NOD stimulation, WEHI-345 prevents cytokine production in vitro and in vivo and ameliorates experimental autoimmune encephalomyelitis in mice.
Hodoodo Cat#: H526614
Name: WEHI-345
CAS#: 1354825-58-3
Chemical Formula: C22H23N7O
Exact Mass: 401.20
Molecular Weight: 401.474
Elemental Analysis: C, 65.82; H, 5.77; N, 24.42; O, 3.99
Synonym: WEHI-345; WEHI345; WEHI 345.
IUPAC/Chemical Name: N-(2-(4-amino-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropyl)isonicotinamide
InChi Key: LEBSTCDZKUSVOY-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H23N7O/c1-14-4-6-15(7-5-14)18-17-19(23)26-13-27-20(17)29(28-18)22(2,3)12-25-21(30)16-8-10-24-11-9-16/h4-11,13H,12H2,1-3H3,(H,25,30)(H2,23,26,27)
SMILES Code: O=C(NCC(C)(N1N=C(C2=CC=C(C)C=C2)C3=C(N)N=CN=C31)C)C4=CC=NC=C4
Appearance: Solid powder
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, not in water
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
More Info:
| Biological target: | WEHI-345 is a RIPK2 kinase inhibitor with an IC50 of 0.13 μM, which delays RIPK2 ubiquitylation and NF-κB activation on oligomerization domain (NOD) stimulation. |
| In vitro activity: | This study has identified a novel RIPK2 kinase inhibitor, WEHI-345, which has greater specificity than previously described small-molecule kinase inhibitors, such as Erlotinib or SB-203580 that were designed to inhibit other kinases but which show some activity against RIPK2. Unbiased analysis of targets of WEHI-345 in cells and a KINOMEscan revealed that WEHI-345 has exquisite specificity for RIPK2. WEHI-345 inhibits RIPK2 activity in vitro with an IC50 of 134 nM, while IC50 against other RIP Kinases is greater than 10 μM. Treatment with WEHI-345 significantly inhibited IL-6 secretion from Raw 267.4 cells at 50 nM, showing a 10-fold stronger inhibition than erlotinib and gefitinib in an identical assay. In cells, WEHI-345 blocked NOD-dependent cytokine production but spared necroptosis signalling mediated by RIPK1 and RIPK3. Reference: Nat Commun. 2015 Mar 17;6:6442. https://www.nature.com/articles/ncomms7442 |
| In vivo activity: | Finally, this study tested WEHI-345 in the K7M2 mouse model. WEHI-345 is the only selective RIPK2 inhibitor that has been utilized in a mouse model, with an MTD of 25 mg/kgWEHI-345 was administered intraperitoneally twice daily at 10 mg/kg. Even at this relatively low dose, RIPK2 inhibition strongly reduced the formation of pulmonary nodules (Fig. 6H). Metastatic burden was also reduced following WEHI-345 treatment, with an effect size similar to that seen in the pulmonary nodules; however, due the variability within the control group, this result did not achieve statistical significance (Fig. 6I). Reference: Mol Cancer Ther. 2020 Jun;19(6):1340-1350. https://pubmed.ncbi.nlm.nih.gov/32371577/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 13.5 | 33.63 | |
| DMF | 2.0 | 4.98 |
The following data is based on the product molecular weight 401.47 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: | 1. Maloney C, Kallis MP, Edelman M, Tzanavaris C, Lesser M, Soffer SZ, Symons M, Steinberg BM. Gefitinib Inhibits Invasion and Metastasis of Osteosarcoma via Inhibition of Macrophage Receptor Interacting Serine-Threonine Kinase 2. Mol Cancer Ther. 2020 Jun;19(6):1340-1350. doi: 10.1158/1535-7163.MCT-19-0903. Epub 2020 May 5. PMID: 32371577. 3. Maloney C, Kallis MP, Edelman M, Tzanavaris C, Lesser M, Soffer SZ, Symons M, Steinberg BM. Gefitinib Inhibits Invasion and Metastasis of Osteosarcoma via Inhibition of Macrophage Receptor Interacting Serine-Threonine Kinase 2. Mol Cancer Ther. 2020 Jun;19(6):1340-1350. doi: 10.1158/1535-7163.MCT-19-0903. Epub 2020 May 5. PMID: 32371577. 4. Nachbur U, Stafford CA, Bankovacki A, Zhan Y, Lindqvist LM, Fiil BK, Khakham Y, Ko HJ, Sandow JJ, Falk H, Holien JK, Chau D, Hildebrand J, Vince JE, Sharp PP, Webb AI, Jackman KA, Mühlen S, Kennedy CL, Lowes KN, Murphy JM, Gyrd-Hansen M, Parker MW, Hartland EL, Lew AM, Huang DC, Lessene G, Silke J. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production. Nat Commun. 2015 Mar 17;6:6442. doi: 10.1038/ncomms7442. PMID: 25778803. |
| In vitro protocol: | 1. Maloney C, Kallis MP, Edelman M, Tzanavaris C, Lesser M, Soffer SZ, Symons M, Steinberg BM. Gefitinib Inhibits Invasion and Metastasis of Osteosarcoma via Inhibition of Macrophage Receptor Interacting Serine-Threonine Kinase 2. Mol Cancer Ther. 2020 Jun;19(6):1340-1350. doi: 10.1158/1535-7163.MCT-19-0903. Epub 2020 May 5. PMID: 32371577. |
| In vivo protocol: | 1. Maloney C, Kallis MP, Edelman M, Tzanavaris C, Lesser M, Soffer SZ, Symons M, Steinberg BM. Gefitinib Inhibits Invasion and Metastasis of Osteosarcoma via Inhibition of Macrophage Receptor Interacting Serine-Threonine Kinase 2. Mol Cancer Ther. 2020 Jun;19(6):1340-1350. doi: 10.1158/1535-7163.MCT-19-0903. Epub 2020 May 5. PMID: 32371577. 2. Nachbur U, Stafford CA, Bankovacki A, Zhan Y, Lindqvist LM, Fiil BK, Khakham Y, Ko HJ, Sandow JJ, Falk H, Holien JK, Chau D, Hildebrand J, Vince JE, Sharp PP, Webb AI, Jackman KA, Mühlen S, Kennedy CL, Lowes KN, Murphy JM, Gyrd-Hansen M, Parker MW, Hartland EL, Lew AM, Huang DC, Lessene G, Silke J. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production. Nat Commun. 2015 Mar 17;6:6442. doi: 10.1038/ncomms7442. PMID: 25778803. |
1: Nachbur U, Stafford CA, Bankovacki A, Zhan Y, Lindqvist LM, Fiil BK, Khakham
Y, Ko HJ, Sandow JJ, Falk H, Holien JK, Chau D, Hildebrand J, Vince JE, Sharp PP,
Webb AI, Jackman KA, Mühlen S, Kennedy CL, Lowes KN, Murphy JM, Gyrd-Hansen M,
Parker MW, Hartland EL, Lew AM, Huang DC, Lessene G, Silke J. A RIPK2 inhibitor
delays NOD signalling events yet prevents inflammatory cytokine production. Nat
Commun. 2015 Mar 17;6:6442. doi: 10.1038/ncomms7442. PubMed PMID: 25778803.
