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PP2 (kinase inhibitor): Difference between revisions

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{{Chembox {{Chembox
| Verifiedfields = changed
⚫ | verifiedrevid = 387924516
| Watchedfields = changed
⚫ | verifiedrevid = 429769063
| ImageFile = PP2 skeletal.svg | ImageFile = PP2 skeletal.svg
| ImageSize = | ImageSize = 120px
| ImageAlt = | ImageAlt =
| Name = PP2
| IUPACName = (4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolopyrimidine | PIN = 1-''tert''-Butyl-3-(4-chlorophenyl)-1''H''-pyrazolopyrimidin-4-amine
| OtherNames = | OtherNames =
| Section1 = {{Chembox Identifiers |Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|??}}
| CASNo = 172889-27-9
| PubChem = 4878 | CASNo = 172889-27-9
| PubChem = 4878
⚫ | SMILES = Nc2ncnc(c12)n(C(C)(C)C)nc1-c3ccc(Cl)cc3
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
⚫ | InChI = 1S/C15H16ClN5/c1-15(2,3)21-14-11(13(17)18-8-19-14)12(20-21)9-4-6-10(16)7-5-9/h4-8H,1-3H3,(H2,17,18,19)}}
| ChemSpiderID = 4712
⚫ | Section2 = {{Chembox Properties
| UNII_Ref = {{fdacite|correct|FDA}}
⚫ | C=15 | H=16 | Cl=1 | N=5
| UNII = PK8JPC58XB
| MolarMass = 301.774
| ChEBI = 78331
⚫ | Appearance = white to off-white solid
⚫ | SMILES = Nc2ncnc(c12)n(C(C)(C)C)nc1-c3ccc(Cl)cc3
⚫ | Density =
⚫ | InChI = 1S/C15H16ClN5/c1-15(2,3)21-14-11(13(17)18-8-19-14)12(20-21)9-4-6-10(16)7-5-9/h4-8H,1-3H3,(H2,17,18,19)}}
⚫ | MeltingPt =
⚫ |Section2={{Chembox Properties
| BoilingPt =
⚫ | C=15 | H=16 | Cl=1 | N=5
| Solubility =
⚫ | Appearance = White to off-white solid
⚫ | SolubleOther = 25 mg/ml
⚫ | Density =
⚫ | Solvent = ]}}
⚫ | MeltingPt =
⚫ | Section3 = {{Chembox Hazards
| MainHazards = | BoilingPt =
| FlashPt = | Solubility =
⚫ | SolubleOther = 25 mg/ml
| Autoignition = }}
⚫ | Solvent = ]}}
⚫ |Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}} }}
'''PP2''' is a substance used in cancer research as a selective ] for ]s. It strongly inhibits the kinases ] (]=4&nbsp;]), ] (5&nbsp;nM) and ] (5&nbsp;nM), shows weaker inhibition of ] (480&nbsp;nM) and practically no inhibition of ] (100&nbsp;µM) and ] (50&nbsp;µM).<ref>{{cite journal|pmid=8557675|year=1996|last1=Hanke|first1=JH|last2=Gardner|first2=JP|last3=Dow|first3=RL|last4=Changelian|first4=PS|last5=Brissette|first5=WH|last6=Weringer|first6=EJ|last7=Pollok|first7=BA|last8=Connelly|first8=PA|title=Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation|volume=271|issue=2|pages=695–701|journal=The Journal of biological chemistry|doi=10.1074/jbc.271.2.695}}</ref><ref>{{cite journal|doi=10.1074/jbc.275.18.13789|pmid=10788500|year=2000|last1=Chen|first1=JK|last2=Capdevila|first2=J|last3=Harris|first3=RC|title=Overexpression of C-terminal Src kinase blocks 14, 15-epoxyeicosatrienoic acid-induced tyrosine phosphorylation and mitogenesis|volume=275|issue=18|pages=13789–92|journal=The Journal of biological chemistry}}</ref><ref>{{cite journal|doi=10.1074/jbc.275.16.11706|pmid=10766791|year=2000|last1=Yoshizumi|first1=M|last2=Abe|first2=J|last3=Haendeler|first3=J|last4=Huang|first4=Q|last5=Berk|first5=BC|title=Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species|volume=275|issue=16|pages=11706–12|journal=The Journal of biological chemistry}}</ref><ref>{{cite journal|doi=10.1210/jc.2002-021278|pmid=12679489|year=2003|last1=Carlomagno|first1=F|last2=Vitagliano|first2=D|last3=Guida|first3=T|last4=Basolo|first4=F|last5=Castellone|first5=MD|last6=Melillo|first6=RM|last7=Fusco|first7=A|last8=Santoro|first8=M|title=Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo3,4-dpyrimidine (PP2)|volume=88|issue=4|pages=1897–902|journal=The Journal of clinical endocrinology and metabolism }}</ref> '''PP2''' is a substance that has frequently been used in cancer research as a "selective" ] for ]s. It strongly inhibits the kinases ] (]=4&nbsp;]), ] (5&nbsp;nM) and ] (5&nbsp;nM), shows weaker inhibition of ] (480&nbsp;nM) and practically no inhibition of ] (100&nbsp;μM) and ] (50&nbsp;μM).<ref>{{cite journal|pmid=8557675|year=1996|last1=Hanke|first1=JH|last2=Gardner|first2=JP|last3=Dow|first3=RL|last4=Changelian|first4=PS|last5=Brissette|first5=WH|last6=Weringer|first6=EJ|last7=Pollok|first7=BA|last8=Connelly|first8=PA|title=Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation|volume=271|issue=2|pages=695–701|journal=The Journal of Biological Chemistry|doi=10.1074/jbc.271.2.695|doi-access=free}}</ref><ref>{{cite journal|doi=10.1074/jbc.275.18.13789|pmid=10788500|year=2000|last1=Chen|first1=JK|last2=Capdevila|first2=J|last3=Harris|first3=RC|title=Overexpression of C-terminal Src kinase blocks 14, 15-epoxyeicosatrienoic acid-induced tyrosine phosphorylation and mitogenesis|volume=275|issue=18|pages=13789–92|journal=The Journal of Biological Chemistry|doi-access=free}}</ref><ref>{{cite journal|doi=10.1074/jbc.275.16.11706|pmid=10766791|year=2000|last1=Yoshizumi|first1=M|last2=Abe|first2=J|last3=Haendeler|first3=J|last4=Huang|first4=Q|last5=Berk|first5=BC|title=Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species|volume=275|issue=16|pages=11706–12|journal=The Journal of Biological Chemistry|doi-access=free}}</ref><ref>{{cite journal|doi=10.1210/jc.2002-021278|pmid=12679489|year=2003|last1=Carlomagno|first1=F|last2=Vitagliano|first2=D|last3=Guida|first3=T|last4=Basolo|first4=F|last5=Castellone|first5=MD|last6=Melillo|first6=RM|last7=Fusco|first7=A|last8=Santoro|first8=M|title=Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo3,4-dpyrimidine (PP2)|volume=88|issue=4|pages=1897–902|journal=The Journal of Clinical Endocrinology and Metabolism |doi-access=free}}</ref> Despite its extensive use as a Src-selective inhibitor, recent research has shown that PP2 is non-selective and inhibits many other kinases with similar affinities.<ref>{{cite journal|doi=10.1021/cb300172e|pmid=22594480|year=2012|last1=Brandvold|first1=KR|last2=Steffey|first2=ME|last3=Fox|first3=CC|last4=Soellner|first4=MB|title=Development of a Highly Selective c-Src Kinase Inhibitor|volume=ASAP|pages=1393–1398|journal=ACS Chemical Biology|issue=8 |pmc=3423592}}</ref>


==References== ==References==
{{reflist|2}} {{Reflist}}


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{{biochemistry-stub}} {{biochemistry-stub}}

Latest revision as of 08:36, 9 September 2024

PP2
Names
Preferred IUPAC name 1-tert-Butyl-3-(4-chlorophenyl)-1H-pyrazolopyrimidin-4-amine
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C15H16ClN5/c1-15(2,3)21-14-11(13(17)18-8-19-14)12(20-21)9-4-6-10(16)7-5-9/h4-8H,1-3H3,(H2,17,18,19)
SMILES
  • Nc2ncnc(c12)n(C(C)(C)C)nc1-c3ccc(Cl)cc3
Properties
Chemical formula C15H16ClN5
Molar mass 301.78 g·mol
Appearance White to off-white solid
Solubility in DMSO 25 mg/ml
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). ☒N verify (what is  ?) Infobox references
Chemical compound

PP2 is a substance that has frequently been used in cancer research as a "selective" inhibitor for Src-family kinases. It strongly inhibits the kinases Lck (IC50=4 nM), Fyn (5 nM) and Hck (5 nM), shows weaker inhibition of EGFR (480 nM) and practically no inhibition of ZAP-70 (100 μM) and JAK2 (50 μM). Despite its extensive use as a Src-selective inhibitor, recent research has shown that PP2 is non-selective and inhibits many other kinases with similar affinities.

References

  1. Hanke, JH; Gardner, JP; Dow, RL; Changelian, PS; Brissette, WH; Weringer, EJ; Pollok, BA; Connelly, PA (1996). "Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation". The Journal of Biological Chemistry. 271 (2): 695–701. doi:10.1074/jbc.271.2.695. PMID 8557675.
  2. Chen, JK; Capdevila, J; Harris, RC (2000). "Overexpression of C-terminal Src kinase blocks 14, 15-epoxyeicosatrienoic acid-induced tyrosine phosphorylation and mitogenesis". The Journal of Biological Chemistry. 275 (18): 13789–92. doi:10.1074/jbc.275.18.13789. PMID 10788500.
  3. Yoshizumi, M; Abe, J; Haendeler, J; Huang, Q; Berk, BC (2000). "Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species". The Journal of Biological Chemistry. 275 (16): 11706–12. doi:10.1074/jbc.275.16.11706. PMID 10766791.
  4. Carlomagno, F; Vitagliano, D; Guida, T; Basolo, F; Castellone, MD; Melillo, RM; Fusco, A; Santoro, M (2003). "Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo3,4-dpyrimidine (PP2)". The Journal of Clinical Endocrinology and Metabolism. 88 (4): 1897–902. doi:10.1210/jc.2002-021278. PMID 12679489.
  5. Brandvold, KR; Steffey, ME; Fox, CC; Soellner, MB (2012). "Development of a Highly Selective c-Src Kinase Inhibitor". ACS Chemical Biology. ASAP (8): 1393–1398. doi:10.1021/cb300172e. PMC 3423592. PMID 22594480.


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