AEW-541 free base
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MedKoo CAT#: 204210

CAS#: 475489-16-8 (free base)

Description: AEW541, also known as NVP-AEW541, is a novel, potent IGF-IR kinase inhibitor. NVP-AEW541 is capable of distinguishing between the IGF-IR (IC50 = 0.086 microM) and the closely related InsR (IC50 = 2.3 microM) in cells. NVP- AEW541 abrogates IGF-I-mediated survival and colony formation in soft agar at concentrations that are consistent with inhibition of IGF-IR autophosphorylation. Note: AEW541 has a Cis-configuration on the cyclobutane ring. Its CAS# is 475489-16-8. Many vendors and Sc-finder scholar made mistake - AEW541 was mistakenly listed as CAS#475488-34-7, the trans-isomer of AEW541. The correct structure of AEW541 can be confirmed from Joel Slade, et al (from Novartis), Org. Process Res. Dev. 2007, 11, 5, 825–835.

Chemical Structure

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AEW-541 free base
CAS# 475489-16-8 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 204210
Name: AEW-541 free base
CAS#: 475489-16-8 (free base)
Chemical Formula: C27H29N5O
Exact Mass: 439.24
Molecular Weight: 439.550
Elemental Analysis: C, 73.78; H, 6.65; N, 15.93; O, 3.64

Price and Availability

Size Price Availability Quantity
10mg USD 190 Ready to ship
25mg USD 350 Ready to ship
50mg USD 550 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3950 Ready to ship
2g USD 6350 Ready to ship
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Related CAS #: 2320261-63-8 (HCl)   475489-16-8 (free base)   475488-34-7 (trans-isomer free base)   1618643-96-1 (trans-isomer HCl)   AEW541 mesylate  

Synonym: NVP-AEW541; NVP-AEW 541; NVP-AEW-541; AEW-541; AEW 541; AEW541;

IUPAC/Chemical Name: 7-((1s,3s)-3-(azetidin-1-ylmethyl)cyclobutyl)-5-(3-(benzyloxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

InChi Key: AECDBHGVIIRMOI-GRGXKFILSA-N

InChi Code: InChI=1S/C27H29N5O/c28-26-25-24(21-8-4-9-23(14-21)33-17-19-6-2-1-3-7-19)16-32(27(25)30-18-29-26)22-12-20(13-22)15-31-10-5-11-31/h1-4,6-9,14,16,18,20,22H,5,10-13,15,17H2,(H2,28,29,30)/t20-,22+

SMILES Code: NC1=C2C(N([C@H]3C[C@@H](CN4CCC4)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

More Info: In vivo, this orally bioavailable compound inhibits IGF-IR signaling in tumor xenografts and significantly reduces the growth of IGF-IR-driven fibrosarcomas. Thus, NVP- AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application.

Biological target: NVP-AEW541 (AEW541) is a potent inhibitor of IGF-1R with IC50 of 0.15 μM as well as inhibits InsR, with IC50 of 0.14 μM.
In vitro activity: To confirm the inhibitory activity of NVP-AEW541 toward IGF-IR kinase and signaling, starved TC-71 cells were treated with doses of 300 nmol/L and 1 μmol/L for 2 hours followed by stimulation with IGF-I for 5 to 30 minutes. Figure 1A shows that both IGF-IR autophosphorylation and the two major IGF-IR-related intracellular signaling pathways, MAPK and PI3K pathways, are completely inhibited by NVP-AEW541. Selective effects of NVP-AEW541 were also confirmed on IGF-I-stimulated Ewing's sarcoma proliferation. Despite the presence of the autocrine loop, Ewing's sarcoma cells maintained the ability to respond to exogenous IGF-I by moderately increasing their proliferation. Inhibitory effects of NVP-AEW541 were maintained and IGF-I could not rescue cells from growth inhibition induced by the compound ( Fig. 1B). Consequently, we determined whether a daily in vitro administration of NVP-AEW541 gave a benefit in terms of growth inhibition. Figure 2B shows that similar inhibitory effects were obtained in TC-71 cells with single or a repeated treatment using NVP-AEW541. This indicates that the stable inhibition of PI3K pathway is sufficient to guarantee remarkable growth inhibitory effects of NVP-AEW541. Growth inhibitory activity of the compound was maintained for at least 72 hours after its removal (33% of growth inhibition with the dose of 300 nmol/L and 50.3% of growth inhibition with the dose of 1 μmol/L; P < 0.05). In conclusion, it is shown that the availability of the selective IGF-IR kinase inhibitor NVP-AEW541 may be a promising approach in the treatment of Ewing's sarcoma Reference: Cancer Res. 2005 May 1;65(9):3868-76. https://pubmed.ncbi.nlm.nih.gov/15867386/
In vivo activity: To evaluate the antitumor activity of NVP-AEW541 in vivo, xenotransplantation experiments were carried out by injecting s.c. HTLA-230 and SK-N-BE2c cells in nude mice. Twenty million cells were injected in the flank of mice that were divided in two groups (eight mice per group). Tumors were grown until the mean volume reached ∼100 mm3 (8-10 days). NVP-AEW541 was administered by oral gavage [50 mg/kg in 0.2 mL of 25 mmol/L l-(+)-tartaric acid] twice a day for 14 consecutive days. In both cases, NVP-AEW541 treatment caused tumor shrinkage (Fig. 3A and C ) that reached the statistical significance (P = 0.0156 and P = 0.0111 for HTLA-230 and SK-N-BE2c, respectively). Signs of systemic toxicity (lethargy, disturbances in feeding behavior) were not observed by daily monitoring during treatment. Animal weight was not significantly different in treated and untreated animals (Fig. 3B and D). Tumors from controls were highly cellular and with a rich network of blood microvessels (Fig. 4A, B, E, and F ); conversely, tumors from NVP-AEW541–treated animals showed many pyknotic cells with frequent presence of micronuclei and scant or no microvascularization (Fig. 4C, D, G, and H). A strong membrane-associated staining pattern was detectable in tumors from controls, whereas tumors from NVP-AEW541–treated animals were mostly negative (Fig. 5 , compare A, B, E, and F with C, D, G, and H). Taken together, these data indicate that NVP-AEW541 can be considered as a novel promising candidate for treatment of neuroblastoma patients. Reference: Clin Cancer Res. 2006 Nov 15;12(22):6772-80. https://pubmed.ncbi.nlm.nih.gov/17121898/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 113.75

Preparing Stock Solutions

The following data is based on the product molecular weight 439.55 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.

Recalculate based on batch purity %
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. Tanno B, Mancini C, Vitali R, Mancuso M, McDowell HP, Dominici C, Raschellà G. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. doi: 10.1158/1078-0432.CCR-06-1479. PMID: 17121898. 2. Scotlandi K, Manara MC, Nicoletti G, Lollini PL, Lukas S, Benini S, Croci S, Perdichizzi S, Zambelli D, Serra M, GarcíaEcheverría C, Hofmann F, Picci P. Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res. 2005 May 1;65(9):3868-76. doi: 10.1158/0008-5472.CAN-04-3192. PMID: 15867386. 3. García-Echeverría C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro HG, Cozens R, Evans DB, Fabbro D, Furet P, Porta DG, Liebetanz J, Martiny-Baron G, Ruetz S, Hofmann F. In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell. 2004 Mar;5(3):231-9. doi: 10.1016/s1535-6108(04)00051-0. PMID: 15050915.
In vitro protocol: 1. Tanno B, Mancini C, Vitali R, Mancuso M, McDowell HP, Dominici C, Raschellà G. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. doi: 10.1158/1078-0432.CCR-06-1479. PMID: 17121898. 2. Scotlandi K, Manara MC, Nicoletti G, Lollini PL, Lukas S, Benini S, Croci S, Perdichizzi S, Zambelli D, Serra M, GarcíaEcheverría C, Hofmann F, Picci P. Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res. 2005 May 1;65(9):3868-76. doi: 10.1158/0008-5472.CAN-04-3192. PMID: 15867386.
In vivo protocol: 1. Tanno B, Mancini C, Vitali R, Mancuso M, McDowell HP, Dominici C, Raschellà G. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. doi: 10.1158/1078-0432.CCR-06-1479. PMID: 17121898. 2. García-Echeverría C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro HG, Cozens R, Evans DB, Fabbro D, Furet P, Porta DG, Liebetanz J, Martiny-Baron G, Ruetz S, Hofmann F. In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell. 2004 Mar;5(3):231-9. doi: 10.1016/s1535-6108(04)00051-0. PMID: 15050915.

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1: Tsushima H, Yamada K. Effects of adipokine administration to the hypothalamic preoptic area on body temperature in rats. J Pharmacol Sci. 2020 Oct;144(2):61-68. doi: 10.1016/j.jphs.2020.07.005. Epub 2020 Jul 10. PMID: 32684333.


2: Liu S, Wu M, Hua Q, Lu D, Tian Y, Yu H, Cheng L, Chen Y, Cao J, Hu X, Tan F. Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain. Parasit Vectors. 2020 May 11;13(1):242. doi: 10.1186/s13071-020-04094-2. PMID: 32393321; PMCID: PMC7216583.


3: Cannarella R, Arato I, Condorelli RA, Luca G, Barbagallo F, Alamo A, Bellucci C, Lilli C, La Vignera S, Calafiore R, Mancuso F, Calogero AE. The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells. J Clin Med. 2019 Apr 27;8(5):577. doi: 10.3390/jcm8050577. PMID: 31035547; PMCID: PMC6571966.


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14: Gohr K, Hamacher A, Engelke LH, Kassack MU. Inhibition of PI3K/Akt/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38. BMC Cancer. 2017 Nov 3;17(1):711. doi: 10.1186/s12885-017-3695-5. PMID: 29100507; PMCID: PMC5670521.


15: May CD, Landers SM, Bolshakov S, Ma X, Ingram DR, Kivlin CM, Watson KL, Sannaa GAA, Bhalla AD, Wang WL, Lazar AJ, Torres KE. Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma. Cancer Biol Ther. 2017 Oct 3;18(10):816-826. doi: 10.1080/15384047.2017.1373230. Epub 2017 Nov 3. Erratum in: Cancer Biol Ther. 2018 Feb 1;19(2):138. PMID: 29099264; PMCID: PMC5678691.


16: Hamilton N, Austin D, Márquez-Garbán D, Sanchez R, Chau B, Foos K, Wu Y, Vadgama J, Pietras R. Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer. Int J Mol Sci. 2017 Nov 2;18(11):2305. doi: 10.3390/ijms18112305. PMID: 29099049; PMCID: PMC5713274.


17: Neuzillet Y, Chapeaublanc E, Krucker C, De Koning L, Lebret T, Radvanyi F, Bernard-Pierrot I. IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer. BMC Cancer. 2017 Sep 7;17(1):636. doi: 10.1186/s12885-017-3618-5. PMID: 28882129; PMCID: PMC5588742.


18: Oberthür R, Seemann H, Gehrig J, Rave-Fränk M, Bremmer F, Halpape R, Conradi LC, Scharf JG, Burfeind P, Kaulfuß S. Simultaneous inhibition of IGF1R and EGFR enhances the efficacy of standard treatment for colorectal cancer by the impairment of DNA repair and the induction of cell death. Cancer Lett. 2017 Oct 28;407:93-105. doi: 10.1016/j.canlet.2017.08.009. Epub 2017 Aug 18. PMID: 28823963.


19: Tsushima H, Morimoto S, Fujishiro M, Yoshida Y, Hayakawa K, Hirai T, Miyashita T, Ikeda K, Yamaji K, Takamori K, Takasaki Y, Sekigawa I, Tamura N. Kinase inhibitors of the IGF-1R as a potential therapeutic agent for rheumatoid arthritis. Autoimmunity. 2017 Aug;50(5):329-335. doi: 10.1080/08916934.2017.1344970. Epub 2017 Jul 6. PMID: 28682648.


20: Stanley A, Ashrafi GH, Seddon AM, Modjtahedi H. Synergistic effects of various Her inhibitors in combination with IGF-1R, C-MET and Src targeting agents in breast cancer cell lines. Sci Rep. 2017 Jun 21;7(1):3964. doi: 10.1038/s41598-017-04301-8. PMID: 28638122; PMCID: PMC5479850.