WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 407889
CAS#: 627518-40-5
Description: JNJ-10198409, also known as RWJ-540973, is an inhibitor of PDGF-BB tyrosine kinase with an IC50 value of 4.2 nM. JNJ-10198409 is a competitive antagonist of the ATP binding and hydrolysis at this receptor, resulting in a dose dependent inhibition of tumor growth and angiogenesis.
MedKoo Cat#: 407889
Name: JNJ-10198409
CAS#: 627518-40-5
Chemical Formula: C18H16FN3O2
Exact Mass: 325.1227
Molecular Weight: 325.3434
Elemental Analysis: C, 66.45; H, 4.96; F, 5.84; N, 12.92; O, 9.84
Synonym: JNJ-10198409; JNJ 10198409; JNJ10198409; RWJ-540973; RWJ 540973; RWJ540973.
IUPAC/Chemical Name: N-(3-fluorophenyl)-1,4-dihydro-6,7-dimethoxy-indeno[1,2-c]pyrazol-3-amine
InChi Key: ZDNURMVOKAERHZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H16FN3O2/c1-23-15-7-10-6-14-17(13(10)9-16(15)24-2)21-22-18(14)20-12-5-3-4-11(19)8-12/h3-5,7-9H,6H2,1-2H3,(H2,20,21,22)
SMILES Code: COC1=CC2=C(C=C1OC)CC3=C2NN=C3NC4=CC=CC(F)=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
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
| Biological target: | JNJ-10198409 is a relatively selective, orally active, and ATP competitive PDGF-RTK (platelet-derived growth factor receptor tyrosine kinase) inhibitor (IC50=2 nM). JNJ-10198409 has good activity against PDGFR-β kinase (IC50=4.2 nM) and PDGFR-α kinase (IC50=45 nM). |
| In vitro activity: | JNJ-10198402 (J101) was confirmed as blocking cell proliferation in GNS cells, as no increases in total cell number were recorded. Surprisingly however, J101 was found to induce a ∼7-fold increase in the numbers of mitotic objects scored during a two-day period compared to DMSO controls (Figure 2B). The increase in cells undergoing mitosis without a concomitant increase in total cell numbers (Figure 2C) suggested that mitotic arrest might be triggered in GNS cultures, but not NS cells, following J101 exposure. Reference: PLoS One. 2013 Oct 30;8(10):e77053. https://pubmed.ncbi.nlm.nih.gov/24204733/ |
| In vivo activity: | Hence, this study investigated the in vivo pharmacodynamic activity of JNJ-10198409, a relatively selective inhibitor of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK), in tumor tissues after administering the compound orally in a nude mouse xenograft model of human LoVo colon cancer. Computer-assisted image analysis was then used to directly compare the ratio of ph-PLCgamma1 to pan-PLCgamma1 immunolabeling intensities in serial sections (5 mum) of tumors obtained from vehicle- and JNJ-10198409-treated tumor-bearing mice. This data showed statistically significant, dose-dependent differences in the ph-PLC/pan-PLC ratio among the four treatment groups (vehicle, 25, 50, and 100 mg/kg b.i.d.). These results confirmed this compound's ability to suppress PDGF-RTK downstream signaling in tumor tissues in vivo. Reference: Mol Cancer Ther. 2005 Aug;4(8):1198-204. https://pubmed.ncbi.nlm.nih.gov/16093435/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 6.51 | 20.0 |
The following data is based on the product molecular weight 325.3434 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. Danovi D, Folarin A, Gogolok S, Ender C, Elbatsh AM, Engström PG, Stricker SH, Gagrica S, Georgian A, Yu D, U KP, Harvey KJ, Ferretti P, Paddison PJ, Preston JE, Abbott NJ, Bertone P, Smith A, Pollard SM. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One. 2013 Oct 30;8(10):e77053. doi: 10.1371/journal.pone.0077053. PMID: 24204733; PMCID: PMC3813721. 2. Ho CY, Ludovici DW, Maharoof US, Mei J, Sechler JL, Tuman RW, Strobel ED, Andraka L, Yen HK, Leo G, Li J, Almond H, Lu H, DeVine A, Tominovich RM, Baker J, Emanuel S, Gruninger RH, Middleton SA, Johnson DL, Galemmo RA Jr. (6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells. J Med Chem. 2005 Dec 29;48(26):8163-73. doi: 10.1021/jm050680m. PMID: 16366598. 3. D'Andrea MR, Mei JM, Tuman RW, Galemmo RA, Johnson DL. Validation of in vivo pharmacodynamic activity of a novel PDGF receptor tyrosine kinase inhibitor using immunohistochemistry and quantitative image analysis. Mol Cancer Ther. 2005 Aug;4(8):1198-204. doi: 10.1158/1535-7163.MCT-05-0004. PMID: 16093435. |
| In vitro protocol: | 1. Danovi D, Folarin A, Gogolok S, Ender C, Elbatsh AM, Engström PG, Stricker SH, Gagrica S, Georgian A, Yu D, U KP, Harvey KJ, Ferretti P, Paddison PJ, Preston JE, Abbott NJ, Bertone P, Smith A, Pollard SM. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One. 2013 Oct 30;8(10):e77053. doi: 10.1371/journal.pone.0077053. PMID: 24204733; PMCID: PMC3813721. 2. Ho CY, Ludovici DW, Maharoof US, Mei J, Sechler JL, Tuman RW, Strobel ED, Andraka L, Yen HK, Leo G, Li J, Almond H, Lu H, DeVine A, Tominovich RM, Baker J, Emanuel S, Gruninger RH, Middleton SA, Johnson DL, Galemmo RA Jr. (6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells. J Med Chem. 2005 Dec 29;48(26):8163-73. doi: 10.1021/jm050680m. PMID: 16366598. |
| In vivo protocol: | 1. D'Andrea MR, Mei JM, Tuman RW, Galemmo RA, Johnson DL. Validation of in vivo pharmacodynamic activity of a novel PDGF receptor tyrosine kinase inhibitor using immunohistochemistry and quantitative image analysis. Mol Cancer Ther. 2005 Aug;4(8):1198-204. doi: 10.1158/1535-7163.MCT-05-0004. PMID: 16093435. |
1: Das F, Ghosh-Choudhury N, Venkatesan B, Kasinath BS, Ghosh Choudhury G. PDGF receptor-β uses Akt/mTORC1 signaling node to promote high glucose-induced renal proximal tubular cell collagen I (α2) expression. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F291-F307. doi: 10.1152/ajprenal.00666.2016. Epub 2017 Apr 19. PubMed PMID: 28424212; PubMed Central PMCID: PMC5582895.
2: Danovi D, Folarin A, Gogolok S, Ender C, Elbatsh AM, Engström PG, Stricker SH, Gagrica S, Georgian A, Yu D, U KP, Harvey KJ, Ferretti P, Paddison PJ, Preston JE, Abbott NJ, Bertone P, Smith A, Pollard SM. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One. 2013 Oct 30;8(10):e77053. doi: 10.1371/journal.pone.0077053. eCollection 2013. PubMed PMID: 24204733; PubMed Central PMCID: PMC3813721.
3: Hiram-Bab S, Katz LS, Shapira H, Sandbank J, Gershengorn MC, Oron Y. Platelet-derived growth factor BB mimics serum-induced dispersal of pancreatic epithelial cell clusters. J Cell Physiol. 2014 Jun;229(6):743-51. doi: 10.1002/jcp.24493. PubMed PMID: 24129818.
4: Ghosh D, Lili L, McGrail DJ, Matyunina LV, McDonald JF, Dawson MR. Integral role of platelet-derived growth factor in mediating transforming growth factor-β1-dependent mesenchymal stem cell stiffening. Stem Cells Dev. 2014 Feb 1;23(3):245-61. doi: 10.1089/scd.2013.0240. Epub 2013 Nov 8. PubMed PMID: 24093435; PubMed Central PMCID: PMC3904528.
5: Eichenbaum G, Hsu CP, Subrahmanyam V, Chen J, Scicinski J, Galemmo RA Jr, Tuman RW, Johnson DL. Oral coadministration of β-glucuronidase to increase exposure of extensively glucuronidated drugs that undergo enterohepatic recirculation. J Pharm Sci. 2012 Jul;101(7):2545-56. doi: 10.1002/jps.23113. Epub 2012 Mar 30. PubMed PMID: 22473491.
6: Ball SG, Shuttleworth A, Kielty CM. Inhibition of platelet-derived growth factor receptor signaling regulates Oct4 and Nanog expression, cell shape, and mesenchymal stem cell potency. Stem Cells. 2012 Mar;30(3):548-60. doi: 10.1002/stem.1015. PubMed PMID: 22213560; PubMed Central PMCID: PMC3537888.
7: Dai WG, Dong LC, Li S, Pollock-Dove C, Chen J, Mansky P, Eichenbaum G. Parallel screening approach to identify solubility-enhancing formulations for improved bioavailability of a poorly water-soluble compound using milligram quantities of material. Int J Pharm. 2007 May 4;336(1):1-11. Epub 2006 Nov 17. PubMed PMID: 17178444.
8: Yan Z, Caldwell GW, Gauthier D, Leo GC, Mei J, Ho CY, Jones WJ, Masucci JA, Tuman RW, Galemmo RA Jr, Johnson DL. N-glucuronidation of the platelet-derived growth factor receptor tyrosine kinase inhibitor 6,7-(dimethoxy-2,4-dihydroindeno[1,2-C]pyrazol-3-yl)-(3-fluoro-phenyl)-amine by human UDP-glucuronosyltransferases. Drug Metab Dispos. 2006 May;34(5):748-55. Epub 2006 Feb 2. PubMed PMID: 16455802.
9: Ho CY, Ludovici DW, Maharoof US, Mei J, Sechler JL, Tuman RW, Strobel ED, Andraka L, Yen HK, Leo G, Li J, Almond H, Lu H, DeVine A, Tominovich RM, Baker J, Emanuel S, Gruninger RH, Middleton SA, Johnson DL, Galemmo RA Jr. (6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells. J Med Chem. 2005 Dec 29;48(26):8163-73. PubMed PMID: 16366598.
10: D'Andrea MR, Mei JM, Tuman RW, Galemmo RA, Johnson DL. Validation of in vivo pharmacodynamic activity of a novel PDGF receptor tyrosine kinase inhibitor using immunohistochemistry and quantitative image analysis. Mol Cancer Ther. 2005 Aug;4(8):1198-204. PubMed PMID: 16093435.
