PD-153035 free base | AG-1517 | CAS#153436-54-5 | 183322-45-4 | EGFR inhibitor

MedKoo Cat#: 202174 | Name: PD-153035 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PD153035 is a ATP-competitive EGFR inhibitor with an IC50 and Ki of 25 and 6 pM. PD153035 effectively blocks the enhancement of mitogenesis, induction of early gene expression, and oncogenic transformation that occur in response to EGF receptor stimulation. With human fibroblasts and epidermoid carcinoma cells, PD153035 at nanomolar concentrations rapidly inhibits EGFR autophosphorylation. With breast and ovarian cancer cells, PD153035 not only blocks cell growth via inhibition of EGFR, but also upregulates the expression of the tumor suppressor retinoic acid receptor-beta 2 (RAR-beta2).

Chemical Structure

PD-153035 free base

CAS#153436-54-5 (free base)

Theoretical Analysis

MedKoo Cat#: 202174

Name: PD-153035 free base

CAS#: 153436-54-5 (free base)

Chemical Formula: C16H14BrN3O2

Exact Mass: 359.0269

Molecular Weight: 360.21

Elemental Analysis: C, 53.35; H, 3.92; Br, 22.18; N, 11.67; O, 8.88

Price and Availability

Size	Price	Availability
100mg	USD 450.00	2 Weeks
200mg	USD 750.00	2 Weeks
500mg	USD 1,450.00	2 Weeks
1g	USD 2,450.00	2 Weeks
2g	USD 3,850.00	2 Weeks

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Related CAS #

153436-54-5 (free base) 183322-45-4 (HCl) 205195-07-9 (xHCl) 586347-97-9 (nitrate)

Synonym

PD-153035; PD 153035; PD153035; SU-5271; SU 5271; SU5271; AG-1517; AG 1517; AG1517; NSC 669364; NSC-669364; NSC669364; WHIP 79.

IUPAC/Chemical Name

N-(3-bromophenyl)-6,7-dimethoxyquinazolin-4-amine

InChi Key

LSPANGZZENHZNJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H14BrN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)

SMILES Code

COC1=CC2=NC=NC(NC3=CC=CC(Br)=C3)=C2C=C1OC

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 soluble in water.

Shelf Life

>5 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

Related CAS# 183322-45-4 (PD153035 HCl) 153436-54-5 (PD153035 free base)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PD153035 (SU-5271; AG1517; ZM 252868) is a potent EGFR inhibitor with Ki and IC50 of 6 and 25 pM.

In vitro activity:

A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. Reference: Science. 1994 Aug 19;265(5175):1093-5. https://pubmed.ncbi.nlm.nih.gov/8066447/

In vivo activity:

This study investigated whether inhibiting EGFR using the EGFR tyrosine kinase inhibitor (TKI) PD153035 improves NAFLD. These results demonstrate that EGFR was activated in liver tissues from high fat diet (HFD)-induced NAFLD mice. Inhibiting EGFR using PD153035 significantly reduced phosphatidylinositol-3-kinase/protein kinase B signaling and sterol responsive elementary binding protein 1 and 2 expression, which prevented HFD-induced hepatic steatosis and hypercholesterolemia by reducing de novo lipogenesis and cholesterol synthesis and enhancing fatty acid oxidation. Reference: PLoS One. 2019 Feb 8;14(2):e0210828. https://pubmed.ncbi.nlm.nih.gov/30735525/

	Solvent	mg/mL	mM
Solubility
	DMF	0.3	0.83
	DMSO	13.8	38.25
	DMSO:PBS (pH 7.2) (1:8)	0.1	0.31
	Ethanol	0.6	1.54

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 360.21 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. Bos M, Mendelsohn J, Kim YM, Albanell J, Fry DW, Baselga J. PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner. Clin Cancer Res. 1997 Nov;3(11):2099-106. PMID: 9815602. 2. Fry DW, Kraker AJ, McMichael A, Ambroso LA, Nelson JM, Leopold WR, Connors RW, Bridges AJ. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science. 1994 Aug 19;265(5175):1093-5. doi: 10.1126/science.8066447. PMID: 8066447. 3. Choung S, Kim JM, Joung KH, Lee ES, Kim HJ, Ku BJ. Epidermal growth factor receptor inhibition attenuates non-alcoholic fatty liver disease in diet-induced obese mice. PLoS One. 2019 Feb 8;14(2):e0210828. doi: 10.1371/journal.pone.0210828. PMID: 30735525; PMCID: PMC6368280. 4. Kenessey I, Kramer Z, István L, Cserepes MT, Garay T, Hegedűs B, Dobos J, Tímár J, Tóvári J. Inhibition of epidermal growth factor receptor improves antitumor efficacy of vemurafenib in BRAF-mutant human melanoma in preclinical model. Melanoma Res. 2018 Dec;28(6):536-546. doi: 10.1097/CMR.0000000000000488. PMID: 30124539.

In vitro protocol:

In vivo protocol:

1. Choung S, Kim JM, Joung KH, Lee ES, Kim HJ, Ku BJ. Epidermal growth factor receptor inhibition attenuates non-alcoholic fatty liver disease in diet-induced obese mice. PLoS One. 2019 Feb 8;14(2):e0210828. doi: 10.1371/journal.pone.0210828. PMID: 30735525; PMCID: PMC6368280. 2. Kenessey I, Kramer Z, István L, Cserepes MT, Garay T, Hegedűs B, Dobos J, Tímár J, Tóvári J. Inhibition of epidermal growth factor receptor improves antitumor efficacy of vemurafenib in BRAF-mutant human melanoma in preclinical model. Melanoma Res. 2018 Dec;28(6):536-546. doi: 10.1097/CMR.0000000000000488. PMID: 30124539.

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PMID: 32822399; PMCID: PMC7444546. 4: Furue K, Ito T, Tsuji G, Nakahara T, Furue M. Scratch wound-induced CXCL8 upregulation is EGFR-dependent in keratinocytes. J Dermatol Sci. 2020 Sep;99(3):209-212. doi: 10.1016/j.jdermsci.2020.07.002. Epub 2020 Jul 15. PMID: 32690371. 5: Suzuki K, Koyanagi-Aoi M, Uehara K, Hinata N, Fujisawa M, Aoi T. Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium. Sci Rep. 2019 Jul 19;9(1):10506. doi: 10.1038/s41598-019-46848-8. PMID: 31324820; PMCID: PMC6642190. 6: Choung S, Kim JM, Joung KH, Lee ES, Kim HJ, Ku BJ. Epidermal growth factor receptor inhibition attenuates non-alcoholic fatty liver disease in diet-induced obese mice. PLoS One. 2019 Feb 8;14(2):e0210828. doi: 10.1371/journal.pone.0210828. PMID: 30735525; PMCID: PMC6368280. 7: Wu X, Du J, Song W, Cao M, Chen S, Xia R. Weak power frequency magnetic fields induce microtubule cytoskeleton reorganization depending on the epidermal growth factor receptor and the calcium related signaling. PLoS One. 2018 Oct 12;13(10):e0205569. doi: 10.1371/journal.pone.0205569. PMID: 30312357; PMCID: PMC6185734. 8: Shu DY, Wojciechowski M, Lovicu FJ. ERK1/2-mediated EGFR-signaling is required for TGFβ-induced lens epithelial-mesenchymal transition. Exp Eye Res. 2019 Jan;178:108-121. doi: 10.1016/j.exer.2018.09.021. Epub 2018 Oct 2. PMID: 30290164. 9: Ronellenfitsch MW, Zeiner PS, Mittelbronn M, Urban H, Pietsch T, Reuter D, Senft C, Steinbach JP, Westphal M, Harter PN. Akt and mTORC1 signaling as predictive biomarkers for the EGFR antibody nimotuzumab in glioblastoma. Acta Neuropathol Commun. 2018 Aug 21;6(1):81. doi: 10.1186/s40478-018-0583-4. PMID: 30129426; PMCID: PMC6102828. 10: Abisoye-Ogunniyan A, Lin H, Ghebremedhin A, Salam AB, Karanam B, Theodore S, Jones-Trich J, Davis M, Grizzle W, Wang H, Yates C. Transcriptional repressor Kaiso promotes epithelial to mesenchymal transition and metastasis in prostate cancer through direct regulation of miR-200c. Cancer Lett. 2018 Sep 1;431:1-10. doi: 10.1016/j.canlet.2018.04.044. Epub 2018 May 8. PMID: 29751044; PMCID: PMC6158022. 11: Zhang GN, Zhang YK, Wang YJ, Gupta P, Ashby CR Jr, Alqahtani S, Deng T, Bates SE, Kaddoumi A, Wurpel JND, Lei YX, Chen ZS. Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: In vitro and in vivo. Cancer Lett. 2018 Jun 28;424:19-29. doi: 10.1016/j.canlet.2018.02.040. Epub 2018 Mar 5. PMID: 29518481. 12: Hartel I, Ronellenfitsch M, Wanka C, Wolking S, Steinbach JP, Rieger J. Activation of AMP-activated kinase modulates sensitivity of glioma cells against epidermal growth factor receptor inhibition. Int J Oncol. 2016 Jul;49(1):173-80. doi: 10.3892/ijo.2016.3498. Epub 2016 Apr 25. PMID: 27121290. 13: Campion CM, Leon Carrion S, Mamidanna G, Sutter CH, Sutter TR, Cole JA. Role of EGF receptor ligands in TCDD-induced EGFR down-regulation and cellular proliferation. Chem Biol Interact. 2016 Jun 25;253:38-47. doi: 10.1016/j.cbi.2016.04.031. Epub 2016 Apr 23. PMID: 27117977; PMCID: PMC4892999. 14: Dai D, Li XF, Wang J, Liu JJ, Zhu YJ, Zhang Y, Wang Q, Xu WG. Predictive efficacy of (11)C-PD153035 PET imaging for EGFR-tyrosine kinase inhibitor sensitivity in non-small cell lung cancer patients. Int J Cancer. 2016 Feb 15;138(4):1003-12. doi: 10.1002/ijc.29832. Epub 2015 Sep 22. PMID: 26334931. 15: Xing RC, Zheng J, Zheng WH, Qin ZP, Liu W, Yao RC. Relevance of E-cadherin expression to EGFR-TKI molecular targeted therapy sensitivity/resistance and its clinical significance. Genet Mol Res. 2015 May 29;14(2):5785-92. doi: 10.4238/2015.May.29.10. PMID: 26125777. 16: Longo A, Librizzi M, Chuckowree IS, Baltus CB, Spencer J, Luparello C. Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA- MB231 Breast Cancer Cells. Molecules. 2015 May 28;20(6):9879-89. doi: 10.3390/molecules20069879. PMID: 26029857; PMCID: PMC6272237. 17: Sakanyan V, Angelini M, Le Béchec M, Lecocq MF, Benaiteau F, Rousseau B, Gyulkhandanyan A, Gyulkhandanyan L, Logé C, Reiter E, Roussakis C, Fleury F. Screening and discovery of nitro-benzoxadiazole compounds activating epidermal growth factor receptor (EGFR) in cancer cells. Sci Rep. 2014 Feb 5;4:3977. doi: 10.1038/srep03977. PMID: 24496106; PMCID: PMC3913914. 18: Leon Carrion S, Sutter CH, Sutter TR. Combined treatment with sodium butyrate and PD153035 enhances keratinocyte differentiation. Exp Dermatol. 2014 Mar;23(3):211-4. doi: 10.1111/exd.12333. PMID: 24451036; PMCID: PMC4046644. 19: Sun J, Cai L, Zhang K, Zhang A, Pu P, Yang W, Gao S. A pilot study on EGFR- targeted molecular imaging of PET/CT With 11C-PD153035 in human gliomas. Clin Nucl Med. 2014 Jan;39(1):e20-6. doi: 10.1097/RLU.0b013e3182a23b73. PMID: 24335566. 20: Lin YC, Wei PL, Tsai YT, Wong JH, Chang CM, Wang JY, Hou MF, Lee YC, Chuang HY, Chang WC. Pb²⁺ induced IL-8 gene expression by extracellular signal- regulated kinases and the transcription factor, activator protein 1, in human gastric carcinoma cells. Environ Toxicol. 2015 Mar;30(3):315-22. doi: 10.1002/tox.21909. Epub 2013 Sep 17. PMID: 24106166.