PD 158780 | CAS#171179-06-9 | EGFR inhibitor

MedKoo Cat#: 532449 | Name: PD 158780

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Description:

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

PD 158780 is a potent in vitro inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) (IC50 0.08 nM), and other members of the erbB family, by competitive binding at the ATP site of these signal transduction enzymes.

Chemical Structure

PD 158780

CAS#171179-06-9

Theoretical Analysis

MedKoo Cat#: 532449

Name: PD 158780

CAS#: 171179-06-9

Chemical Formula: C14H12BrN5

Exact Mass: 329.0276

Molecular Weight: 330.19

Elemental Analysis: C, 50.93; H, 3.66; Br, 24.20; N, 21.21

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
10mg	USD 650.00	2 Weeks

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Related CAS #

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Synonym

PD 158780; PD158780; PD-158780.

IUPAC/Chemical Name

4-N-(3-bromophenyl)-6-N-methylpyrido[3,4-d]pyrimidine-4,6-diamine

InChi Key

KFHMLBXBRCITHF-UHFFFAOYSA-N

InChi Code

InChI=1S/C14H12BrN5/c1-16-13-6-11-12(7-17-13)18-8-19-14(11)20-10-4-2-3-9(15)5-10/h2-8H,1H3,(H,16,17)(H,18,19,20)

SMILES Code

CNC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=N1

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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

PD158780 is a potent EGFR family inhibitor with IC50s of 8 pM, 49, 52, 52 nM for EGFR, ErbB2, ErbB3, and ErbB4.

In vitro activity:

PD 158780 was highly specific for the EGF receptor in Swiss 3T3 fibroblasts, inhibiting EGF-dependent receptor autophosphorylation and thymidine incorporation at low nanomolar concentrations while requiring micromolar levels for platelet-derived growth factor- and basic fibroblast growth factor-dependent processes. PD 158780 inhibited heregulin-stimulated phosphorylation in the SK-BR-3 and MDA-MB-453 breast carcinomas with IC50 values of 49 and 52 nM, respectively, suggesting that the compound was active against other members of the EGF receptor family. Reference: Biochem Pharmacol. 1997 Oct 15;54(8):877-87. https://pubmed.ncbi.nlm.nih.gov/9354588/

In vivo activity:

This study verified the involvement of ErbB signalling in mGluRI-dependent learning processes, by evaluating the consequence of an intrahippocampal in vivo injection of a pan-ErbB inhibitor in the object recognition test in mice, a learning task dependent on hippocampal mGluRI. This study found that NRG1 potentiates mGluRI-dependent functions on pyramidal neurons excitability and synaptic plasticity at CA3-CA1 synapses. Further, endogenous ErbB signalling per se regulates, through mGluRI, neuronal excitability and LTD in CA1 pyramidal neurons, since ErbB inhibition reduces mGluRI-induced neuronal excitation and mGluRI-LTD. In vivo intrahippocampal injection of the ErbB inhibitor, PD158780, impairs mGluRI-LTD at CA3-CA1 synapses and affects the exploratory behavior in the object recognition test. Reference: Pharmacol Res. 2018 Apr;130:12-24. https://pubmed.ncbi.nlm.nih.gov/29427771/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	90.86
	DMSO	19.9	60.25
	Ethanol	5.1	15.52

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 330.19 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. Gonzales AJ, Fry DW. G1 cell cycle arrest due to the inhibition of erbB family receptor tyrosine kinases does not require the retinoblastoma protein. Exp Cell Res. 2005 Feb 1;303(1):56-67. doi: 10.1016/j.yexcr.2004.08.040. PMID: 15572027. 2. Fry DW, Nelson JM, Slintak V, Keller PR, Rewcastle GW, Denny WA, Zhou H, Bridges AJ. Biochemical and antiproliferative properties of 4-[ar(alk)ylamino]pyridopyrimidines, a new chemical class of potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. Biochem Pharmacol. 1997 Oct 15;54(8):877-87. doi: 10.1016/s0006-2952(97)00242-6. PMID: 9354588. 3. Ledonne A, Mango D, Latagliata EC, Chiacchierini G, Nobili A, Nisticò R, D'Amelio M, Puglisi-Allegra S, Mercuri NB. Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory. Pharmacol Res. 2018 Apr;130:12-24. doi: 10.1016/j.phrs.2018.02.003. Epub 2018 Feb 7. PMID: 29427771. 4. Fisahn A, Neddens J, Yan L, Buonanno A. Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia. Cereb Cortex. 2009 Mar;19(3):612-8. doi: 10.1093/cercor/bhn107. Epub 2008 Jul 16. PMID: 18632742; PMCID: PMC2638818.

In vitro protocol:

In vivo protocol:

1. Ledonne A, Mango D, Latagliata EC, Chiacchierini G, Nobili A, Nisticò R, D'Amelio M, Puglisi-Allegra S, Mercuri NB. Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory. Pharmacol Res. 2018 Apr;130:12-24. doi: 10.1016/j.phrs.2018.02.003. Epub 2018 Feb 7. PMID: 29427771. 2. Fisahn A, Neddens J, Yan L, Buonanno A. Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia. Cereb Cortex. 2009 Mar;19(3):612-8. doi: 10.1093/cercor/bhn107. Epub 2008 Jul 16. PMID: 18632742; PMCID: PMC2638818.

1: Geng F, Liu JY, Chen XW, Zou WJ, Wu JL, Rodriguez G, Peng C, Tian J, Lu GF. ErbB4 Receptors in the Medial Habenula Regulate Contextual Fear Memory. Pharmacology. 2019;103(1-2):68-75. doi: 10.1159/000495064. Epub 2018 Dec 4. PMID: 30513516. 2: Izumi Y, Zorumski CF. Neuregulin and Dopamine D4 Receptors Contribute Independently to Depotentiation of Schaffer Collateral LTP by Temperoammonic Path Stimulation. eNeuro. 2017 Aug 21;4(4):ENEURO.0176-17.2017. doi: 10.1523/ENEURO.0176-17.2017. PMID: 28828402; PMCID: PMC5563842. 3: Juretić N, Díaz J, Romero F, González G, Jaimovich E, Riveros N. Interleukin-6 and neuregulin-1 as regulators of utrophin expression via the activation of NRG-1/ErbB signaling pathway in mdx cells. Biochim Biophys Acta Mol Basis Dis. 2017 Mar;1863(3):770-780. doi: 10.1016/j.bbadis.2016.12.008. Epub 2016 Dec 15. PMID: 27988307. 4: Geng F, Zhang J, Wu JL, Zou WJ, Liang ZP, Bi LL, Liu JH, Kong Y, Huang CQ, Li XW, Yang JM, Gao TM. Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior. Neuroscience. 2016 Aug 4;329:182-92. doi: 10.1016/j.neuroscience.2016.05.018. Epub 2016 May 14. PMID: 27189883. 5: Bi LL, Sun XD, Zhang J, Lu YS, Chen YH, Wang J, Geng F, Liu F, Zhang M, Liu JH, Li XW, Mei L, Gao TM. Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors. Neuropsychopharmacology. 2015 Mar;40(4):974-86. doi: 10.1038/npp.2014.274. Epub 2014 Oct 13. PMID: 25308353; PMCID: PMC4330511. 6: Du H, Kwon IK, Kim J. Neuregulin-1 impairs the long-term depression of hippocampal inhibitory synapses by facilitating the degradation of endocannabinoid 2-AG. J Neurosci. 2013 Sep 18;33(38):15022-31. doi: 10.1523/JNEUROSCI.5833-12.2013. PMID: 24048832; PMCID: PMC3776056. 7: Jameson MJ, Taniguchi LE, VanKoevering KK, Stuart MM, Francom CR, Mendez RE, Beckler AD, Carlson HT, Thomas CY, Khalil AA. Activation of the insulin-like growth factor-1 receptor alters p27 regulation by the epidermal growth factor receptor in oral squamous carcinoma cells. J Oral Pathol Med. 2013 Apr;42(4):332-8. doi: 10.1111/jop.12014. Epub 2012 Oct 26. PMID: 23106397; PMCID: PMC3693221. 8: Janssen MJ, Leiva-Salcedo E, Buonanno A. Neuregulin directly decreases voltage-gated sodium current in hippocampal ErbB4-expressing interneurons. J Neurosci. 2012 Oct 3;32(40):13889-95. doi: 10.1523/JNEUROSCI.1420-12.2012. PMID: 23035098; PMCID: PMC3690813. 9: Pick A, Wiese M. Tyrosine kinase inhibitors influence ABCG2 expression in EGFR-positive MDCK BCRP cells via the PI3K/Akt signaling pathway. ChemMedChem. 2012 Apr;7(4):650-62. doi: 10.1002/cmdc.201100543. Epub 2012 Feb 22. PMID: 22354538. 10: Tan GH, Liu YY, Hu XL, Yin DM, Mei L, Xiong ZQ. Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons. Nat Neurosci. 2011 Dec 11;15(2):258-66. doi: 10.1038/nn.3005. PMID: 22158510. 11: Toffoli G, De Mattia E, Cecchin E, Biason P, Masier S, Corona G. Pharmacology of epidermal growth factor inhibitors. Int J Biol Markers. 2007 Jan-Mar;22(1 Suppl 4):S24-39. PMID: 17520578. 12: Patterson TJ, Rice RH. Arsenite and insulin exhibit opposing effects on epidermal growth factor receptor and keratinocyte proliferative potential. Toxicol Appl Pharmacol. 2007 May 15;221(1):119-28. doi: 10.1016/j.taap.2007.02.003. Epub 2007 Feb 14. PMID: 17400267; PMCID: PMC1950287. 13: Chang Q, Fischbach GD. An acute effect of neuregulin 1 beta to suppress alpha 7-containing nicotinic acetylcholine receptors in hippocampal interneurons. J Neurosci. 2006 Nov 1;26(44):11295-303. doi: 10.1523/JNEUROSCI.1794-06.2006. PMID: 17079657; PMCID: PMC6674541. 14: Schaefer KL, Brachwitz K, Braun Y, Diallo R, Wai DH, Zahn S, Schneider DT, Kuhnen C, Vollmann A, Brockhoff G, Gabbert HE, Poremba C. Constitutive activation of neuregulin/ERBB3 signaling pathway in clear cell sarcoma of soft tissue. Neoplasia. 2006 Jul;8(7):613-22. doi: 10.1593/neo.06238. PMID: 16867224; PMCID: PMC1601931. 15: Gu Z, Jiang Q, Fu AK, Ip NY, Yan Z. Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex. J Neurosci. 2005 May 18;25(20):4974-84. doi: 10.1523/JNEUROSCI.1086-05.2005. PMID: 15901778; PMCID: PMC6724849. 16: Kansra S, Stoll SW, Johnson JL, Elder JT. Src family kinase inhibitors block amphiregulin-mediated autocrine ErbB signaling in normal human keratinocytes. Mol Pharmacol. 2005 Apr;67(4):1145-57. doi: 10.1124/mol.104.004689. Epub 2004 Dec 22. PMID: 15615697. 17: Gonzales AJ, Fry DW. G1 cell cycle arrest due to the inhibition of erbB family receptor tyrosine kinases does not require the retinoblastoma protein. Exp Cell Res. 2005 Feb 1;303(1):56-67. doi: 10.1016/j.yexcr.2004.08.040. PMID: 15572027. 18: Midwinter RG, Peskin AV, Vissers MC, Winterbourn CC. Extracellular oxidation by taurine chloramine activates ERK via the epidermal growth factor receptor. J Biol Chem. 2004 Jul 30;279(31):32205-11. doi: 10.1074/jbc.M402070200. Epub 2004 May 27. PMID: 15166244. 19: Roysommuti S, Carroll SL, Wyss JM. Neuregulin-1beta modulates in vivo entorhinal-hippocampal synaptic transmission in adult rats. Neuroscience. 2003;121(3):779-85. doi: 10.1016/s0306-4522(03)00503-7. PMID: 14568036. 20: Frohnert PW, Stonecypher MS, Carroll SL. Constitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell line. Glia. 2003 Aug;43(2):104-18. doi: 10.1002/glia.10232. PMID: 12838503.