Synonym
PD168393; PD 168393; PD-168393.
IUPAC/Chemical Name
4-[(3-Bromophenyl)amino]-6-acrylamidoquinazoline
InChi Key
HTUBKQUPEREOGA-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H13BrN4O/c1-2-16(23)21-13-6-7-15-14(9-13)17(20-10-19-15)22-12-5-3-4-11(18)8-12/h2-10H,1H2,(H,21,23)(H,19,20,22)
SMILES Code
C=CC(NC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=C1)=O
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
Biological target:
PD168393 is a potent, selective and cell-permeable inhibitor of EGFR tyrosine kinase and ErbB2.
In vitro activity:
Stably transfected cell lines overexpressing Her2 or empty vector were generated, and the effect of an EGFR and Her2 selective tyrosine kinase inhibitor, PD168393, on these cells was characterized. Treatment of 3T3-Her2 cells with PD168393 showed rapid and potent inhibition of Her2-induced tyrosine phosphorylation with half-maximal inhibition at ≈100 nM and substantial inhibition at 10 min after drug addition (Fig. 1 B and C).
Reference: Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9773-8. https://pubmed.ncbi.nlm.nih.gov/16785428/
In vivo activity:
The present study evaluated the effects of EGFR inhibitor, PD168393 (PD), on the myelination in mouse contusive SCI model. This study found that expression of myelin basic protein (MBP) in the injured spinal cords of PD treated mice was remarkably elevated. The density of glial precursor cells and oligodendrocytes (OLs) was increased and the cell apoptosis in lesions was attenuated after PD168393 treatment. Moreover, PD168393 treatment reduced both the numbers of OX42 + microglial cells and glial fibrillary acidic protein + astrocytes in damaged area of spinal cords.
Reference: Cell Mol Neurobiol. 2016 Oct;36(7):1169-78. https://pubmed.ncbi.nlm.nih.gov/26883518/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
81.25 |
| DMSO |
38.0 |
102.92 |
| Ethanol |
1.0 |
2.71 |
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
369.22
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. Li ZW, Li JJ, Wang L, Zhang JP, Wu JJ, Mao XQ, Shi GF, Wang Q, Wang F, Zou J. Epidermal growth factor receptor inhibitor ameliorates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury. J Neuroinflammation. 2014 Apr 5;11:71. doi: 10.1186/1742-2094-11-71. PMID: 24708754; PMCID: PMC4030311.
2. Bose R, Molina H, Patterson AS, Bitok JK, Periaswamy B, Bader JS, Pandey A, Cole PA. Phosphoproteomic analysis of Her2/neu signaling and inhibition. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9773-8. doi: 10.1073/pnas.0603948103. Epub 2006 Jun 19. PMID: 16785428; PMCID: PMC1502529.
3. Zhang S, Ju P, Tjandra E, Yeap Y, Owlanj H, Feng Z. Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury. Cell Mol Neurobiol. 2016 Oct;36(7):1169-78. doi: 10.1007/s10571-015-0313-4. Epub 2016 Feb 16. PMID: 26883518.
4. Jiang J, Zhang J, Yao P, Wu X, Li K. Activation of spinal neuregulin 1-ErbB2 signaling pathway in a rat model of cancer-induced bone pain. Int J Oncol. 2014 Jul;45(1):235-44. doi: 10.3892/ijo.2014.2429. Epub 2014 May 9. PMID: 24818668.
In vitro protocol:
1. Li ZW, Li JJ, Wang L, Zhang JP, Wu JJ, Mao XQ, Shi GF, Wang Q, Wang F, Zou J. Epidermal growth factor receptor inhibitor ameliorates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury. J Neuroinflammation. 2014 Apr 5;11:71. doi: 10.1186/1742-2094-11-71. PMID: 24708754; PMCID: PMC4030311.
2. Bose R, Molina H, Patterson AS, Bitok JK, Periaswamy B, Bader JS, Pandey A, Cole PA. Phosphoproteomic analysis of Her2/neu signaling and inhibition. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9773-8. doi: 10.1073/pnas.0603948103. Epub 2006 Jun 19. PMID: 16785428; PMCID: PMC1502529.
In vivo protocol:
1. Zhang S, Ju P, Tjandra E, Yeap Y, Owlanj H, Feng Z. Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury. Cell Mol Neurobiol. 2016 Oct;36(7):1169-78. doi: 10.1007/s10571-015-0313-4. Epub 2016 Feb 16. PMID: 26883518.
2. Jiang J, Zhang J, Yao P, Wu X, Li K. Activation of spinal neuregulin 1-ErbB2 signaling pathway in a rat model of cancer-induced bone pain. Int J Oncol. 2014 Jul;45(1):235-44. doi: 10.3892/ijo.2014.2429. Epub 2014 May 9. PMID: 24818668.
1: da Rocha JF, Bastos L, Domingues SC, Bento AR, Konietzko U, da Cruz E Silva OAB, Vieira SI. APP Binds to the EGFR Ligands HB-EGF and EGF, Acting Synergistically with EGF to Promote ERK Signaling and Neuritogenesis. Mol Neurobiol. 2021 Feb;58(2):668-688. doi: 10.1007/s12035-020-02139-2. Epub 2020 Oct 2. PMID: 33009641.
2: Skelton LA, Boron WF. Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in rabbit renal proximal tubules. Am J Physiol Renal Physiol. 2013 Dec 15;305(12):F1747-64. doi: 10.1152/ajprenal.00307.2013. Epub 2013 Oct 16. PMID: 24133121; PMCID: PMC3882443.
3: Poole NM, Nyindodo-Ogari L, Kramer C, Coons LB, Cole JA. Effects of tick saliva on the migratory and invasive activity of Saos-2 osteosarcoma and MDA- MB-231 breast cancer cells. Ticks Tick Borne Dis. 2013 Feb;4(1-2):120-7. doi: 10.1016/j.ttbdis.2012.09.003. Epub 2012 Nov 16. PMID: 23168047.
4: Turpaev K, Drapier JC. Stimulatory effect of benzylidenemalononitrile tyrphostins on expression of NO-dependent genes in U-937 monocytic cells. Eur J Pharmacol. 2009 Mar 15;606(1-3):1-8. doi: 10.1016/j.ejphar.2009.01.015. Epub 2009 Jan 21. PMID: 19374863.
5: Hammoud L, Burger DE, Lu X, Feng Q. Tissue inhibitor of metalloproteinase-3 inhibits neonatal mouse cardiomyocyte proliferation via EGFR/JNK/SP-1 signaling. Am J Physiol Cell Physiol. 2009 Apr;296(4):C735-45. doi: 10.1152/ajpcell.00246.2008. Epub 2009 Feb 11. PMID: 19211917.
6: Khalil MY, Grandis JR, Shin DM. Targeting epidermal growth factor receptor: novel therapeutics in the management of cancer. Expert Rev Anticancer Ther. 2003 Jun;3(3):367-80. doi: 10.1586/14737140.3.3.367. PMID: 12820779.
7: Sun Y, Fry DW, Vincent P, Nelson JM, Elliott W, Leopold WR. Growth inhibition of nasopharyngeal carcinoma cells by EGF receptor tyrosine kinase inhibitors. Anticancer Res. 1999 Mar-Apr;19(2A):919-24. PMID: 10368634.
