WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202042
CAS#: 475488-23-4
Description: NVP-ADW742, also known as ADW-742 or GSK 552602A, is a novel small weight molecular inhibitor of IGF-IR with potential anticancer activity. NVP-ADW742 inhibited IGF-IR-mediated proliferation with an IC50 of 11.12 µmol/l. NVP-ADW742 induced early suppression of Akt, P38 and GSK-3β phosphorylation. NVP-ADW742 enhanced the chemosensitivity of Daoy to temozolomide in vitro, as a potent anti-tumor agent highly selective against IGF-IR. NVP-ADW742 was found to suppresse survival and resistance to chemotherapy in acute myeloid leukemia cells.
MedKoo Cat#: 202042
Name: ADW742
CAS#: 475488-23-4
Chemical Formula: C28H31N5O
Exact Mass: 453.25286
Molecular Weight: 453.57864
Elemental Analysis: C, 74.14; H, 6.89; N, 15.44; O, 3.53
Synonym: NVP-ADW742; NVP ADW-742; NVP ADW 742; ADW 742; ADW-742; ADW742; GSK 552602A; GSK-552602A; GSK552602A.
IUPAC/Chemical Name: 5-(3-(benzyloxy)phenyl)-7-((1r,3r)-3-(pyrrolidin-1-ylmethyl)cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
InChi Key: LSFLAQVDISHMNB-AFARHQOCSA-N
InChi Code: InChI=1S/C28H31N5O/c29-27-26-25(22-9-6-10-24(15-22)34-18-20-7-2-1-3-8-20)17-33(28(26)31-19-30-27)23-13-21(14-23)16-32-11-4-5-12-32/h1-3,6-10,15,17,19,21,23H,4-5,11-14,16,18H2,(H2,29,30,31)/t21-,23-
SMILES Code: NC1=C2C(N([C@H]3C[C@H](CN4CCCC4)C3)C=C2C5=CC=CC(OCC6=CC=CC=C6)=C5)=NC=N1
Appearance: white 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
| Biological target: | NVP-ADW742 (ADW742) is an IGF-1R tyrosine kinase inhibitor with an IC50 of 0.17 μM that also inhibits insulin receptor (InsR) with an IC50 of 2.8 μM. |
| In vitro activity: | Dose-dependent blockade of basal and IGF1-induced phosphorylation was seen with ADW742 in all cell lines (IC50 of phosphorylation = 171-508 nmol/L). As shown in Fig. 1 and Supplementary Figs. S2-S4, the effects of this compound depended on the levels of IGF1R protein expression and basal phosphorylation of each cell line. Furthermore, AKT pathway activation induced by IGF1 was markedly blocked with the pretreatment with ADW742. Phospho-AKT and p-mTOR (Fig. 1C-D; Supplementary Figs. S2-4) were inhibited in a dose-dependent manner. Sensitivity to the drug showed a positive correlation with the levels of expression and basal phosphorylation of IGF1R. In contrast, MAPK42/44 remained active even when pretreated with high concentrations of ADW742, in all cell lines except A4573. Reference: Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. https://clincancerres.aacrjournals.org/content/12/11/3532.long |
| In vivo activity: | The IGF1-receptor inhibitor NVP-ADW742 (500 μM) or its vehicle control, DMSO (5%), were intraperitoneally injected into zebrafish every 12 h throughout the eight day dark-adaptation period. NVP-ADW742 significantly reduced the number of proliferating cells in the ONL at 8 days of dark-adaptation relative to DMSO controls (Fig. 7A–E; NVP-ADW742: 5.8 ± 1.0, n = 21; DMSO: 10.4 ± 1.4, n = 33, p = 2.5*10−6). In contrast, the low number of INL PCNA-positive cells was not affected by exposure to NVP-ADW742 (NVP-ADW742: 0.13 ± 0.07, n = 21; DMSO: 0.23 ± 0.08, n = 33, p = 0.069). Taken together, these data suggest that dark-adaptation-mediated rod precursor cell proliferation occurred in an IGF1-receptor-dependent manner. Reference: Exp Eye Res. 2019 Jan;178:148-159. https://pubmed.ncbi.nlm.nih.gov/30267656/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.48 | 45.15 | |
| DMF | 30.0 | 66.14 | |
| Ethanol | 12.51 | 27.58 | |
| Ethanol:PBS (pH 7.2) (1:10) | 0.09 | 0.2 |
The following data is based on the product molecular weight 453.57864 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. Martins AS, Mackintosh C, Martín DH, Campos M, Hernández T, Ordóñez JL, de Alava E. Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. doi: 10.1158/1078-0432.CCR-05-1778. PMID: 16740780. 2. Warshamana-Greene GS, Litz J, Buchdunger E, García-Echeverría C, Hofmann F, Krystal GW. The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy. Clin Cancer Res. 2005 Feb 15;11(4):1563-71. doi: 10.1158/1078-0432.CCR-04-1544. PMID: 15746061. 3. Lahne M, Piekos SM, O'Neill J, Ackerman KM, Hyde DR. Photo-regulation of rod precursor cell proliferation. Exp Eye Res. 2019 Jan;178:148-159. doi: 10.1016/j.exer.2018.09.015. Epub 2018 Sep 27. PMID: 30267656. 4. Dent P, Han SI, Mitchell C, Studer E, Yacoub A, Grandis J, Grant S, Krystal GW, Hylemon PB. Inhibition of insulin/IGF-1 receptor signaling enhances bile acid toxicity in primary hepatocytes. Biochem Pharmacol. 2005 Nov 25;70(11):1685-96. doi: 10.1016/j.bcp.2005.08.020. Epub 2005 Oct 3. PMID: 16207485. |
| In vitro protocol: | 1. Martins AS, Mackintosh C, Martín DH, Campos M, Hernández T, Ordóñez JL, de Alava E. Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. doi: 10.1158/1078-0432.CCR-05-1778. PMID: 16740780. 2. Warshamana-Greene GS, Litz J, Buchdunger E, García-Echeverría C, Hofmann F, Krystal GW. The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy. Clin Cancer Res. 2005 Feb 15;11(4):1563-71. doi: 10.1158/1078-0432.CCR-04-1544. PMID: 15746061. |
| In vivo protocol: | 1. Lahne M, Piekos SM, O'Neill J, Ackerman KM, Hyde DR. Photo-regulation of rod precursor cell proliferation. Exp Eye Res. 2019 Jan;178:148-159. doi: 10.1016/j.exer.2018.09.015. Epub 2018 Sep 27. PMID: 30267656. 2. Dent P, Han SI, Mitchell C, Studer E, Yacoub A, Grandis J, Grant S, Krystal GW, Hylemon PB. Inhibition of insulin/IGF-1 receptor signaling enhances bile acid toxicity in primary hepatocytes. Biochem Pharmacol. 2005 Nov 25;70(11):1685-96. doi: 10.1016/j.bcp.2005.08.020. Epub 2005 Oct 3. PMID: 16207485. |
1: Zhou H, Rao J, Lin J, Yin B, Sheng H, Lin F, Zhang N, Yang L. The insulin- like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy. Oncol Rep. 2011 Jun;25(6):1565-71. doi: 10.3892/or.2011.1233. Epub 2011 Mar 23. PMID: 21455580.
2: Martins AS, Mackintosh C, Martín DH, Campos M, Hernández T, Ordóñez JL, de Alava E. Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. doi: 10.1158/1078-0432.CCR-05-1778. PMID: 16740780.
3: Warshamana-Greene GS, Litz J, Buchdunger E, García-Echeverría C, Hofmann F, Krystal GW. The insulin-like growth factor-I receptor kinase inhibitor, NVP- ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy. Clin Cancer Res. 2005 Feb 15;11(4):1563-71. doi: 10.1158/1078-0432.CCR-04-1544. PMID: 15746061.
4: He Y, Zhang J, Zheng J, Du W, Xiao H, Liu W, Li X, Chen X, Yang L, Huang S. The insulin-like growth factor-1 receptor kinase inhibitor, NVP-ADW742, suppresses survival and resistance to chemotherapy in acute myeloid leukemia cells. Oncol Res. 2010;19(1):35-43. doi: 10.3727/096504010x12828372551821. PMID: 21141739.
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20: Dent P, Han SI, Mitchell C, Studer E, Yacoub A, Grandis J, Grant S, Krystal GW, Hylemon PB. Inhibition of insulin/IGF-1 receptor signaling enhances bile acid toxicity in primary hepatocytes. Biochem Pharmacol. 2005 Nov 25;70(11):1685-96. doi: 10.1016/j.bcp.2005.08.020. Epub 2005 Oct 3. PMID: 16207485.
