Details of the BTS | SYNBIP

General Information of Binding Target of SBP (BTS) (ID: ST00138)
BTS Name	GTPase KRas
Synonyms	EC 3.6.5.2; K-Ras 2; Ki-Ras; c-K-ras; c-Ki-ras
BTS Type	Protein
Family	Small GTPase superfamily; Ras family
Gene Name	KRAS
Organism	Homo sapiens (Human)
Function	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity Plays an important role in the regulation of cell proliferation Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner
UniProt ID	P01116
UniProt Entry	RASK_HUMAN
PFam	PF00071
Gene ID	3845
Sequence	MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG QEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDL PSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKISKEEKTPGC VKIKKCIIM
Sequence Length	189

Synthetic Binding Protein (SBP) Targeting This BTS

SBP Name	Highest Status	Mechanism	Affinity	Application	Details	Ref
Bicyclic peptide anti-KRAS B1	Research	inhibitor	Kd: 37 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
Bicyclic peptide anti-KRAS B2	Research	inhibitor	Kd: 0.49 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
Bicyclic peptide anti-KRAS B3	Research	inhibitor	Kd: 2.1 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
Bicyclic peptide anti-KRAS B4	Research	inhibitor	Kd: 2.6 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
Bicyclic peptide anti-KRAS B4-27	Research	Inhibitor	IC50: 690 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[2]
DARPin anti-KRas E3.5	Research	Inhibitor	N.A.	Cancers [ICD-11: 2D4Z]	SBP Info	[3], [4]
DARPin anti-KRas K13	Research	Inhibitor	Kd: 30 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[3]
DARPin anti-KRas K19	Research	Inhibitor	Kd: 10 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[3]
DARPin anti-KRas K27	Research	Inhibitor	Kd: 3.9 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[3], [5]
DARPin anti-KRas K55	Research	Inhibitor	Kd: 167 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[3]
Monobody anti-HRAS/NRAS/KRAS JAM20	Research	Inhibitor	Kd: 7 nM	Tumors [ICD-11: XH1N44]	SBP Info	[6]
Monobody anti-HRAS/NRAS/KRAS JAM20	Research	Inhibitor	Kd: 28 nM	Tumors [ICD-11: XH1N44]	SBP Info	[6]
Monobody anti-HRAS/NRAS/KRAS R15	Research	Inhibitor	Kd: 422 nM	Tools for inhibition of selected oncogenic RAS mutants	SBP Info	[7]
Monobody anti-KRas 12VC1	Research	Inhibitor	Kd: 9600 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[8]
Monobody anti-KRas 12VC1	Research	Inhibitor	Kd: 100 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[8]
Monobody anti-KRas 12VC1	Research	Inhibitor	Kd: 24.7 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[8]
Monobody anti-KRas/HRas NS1	Research	Inhibitor	Kd: 65 nM	Pancreas cancer [ICD-11: 2C10.Z]	SBP Info	[9], [10]

References

1	Direct Ras Inhibitors Identified from a Structurally Rigidified Bicyclic Peptide Library. Tetrahedron. 2014 Oct 21;70(42):7714-7720.
2	Discovery of a Bicyclic Peptidyl Pan-Ras Inhibitor. J Med Chem. 2021 Sep 9;64(17):13038-13053.
3	KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe. Nat Commun. 2019 Jun 13;10(1):2607.
4	Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin. Theranostics. 2017 Jul 8;7(11):2806-2821.
5	Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange. Nat Commun. 2017 Jul 14;8:16111.
6	Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket. Proc Natl Acad Sci U S A. 2022 Oct 25;119(43):e2204481119.
7	Identification of the nucleotide-free state as a therapeutic vulnerability for inhibition of selected oncogenic RAS mutants. Cell Rep. 2022 Feb 8;38(6):110322.
8	Selective and noncovalent targeting of RAS mutants for inhibition and degradation. Nat Commun. 2021 May 11;12(1):2656.
9	Targeting the KRAS 4-5 allosteric interface inhibits pancreatic cancer tumorigenesis. Small GTPases. 2021 May 5;1-14.
10	Targeting the 4-5 interface of RAS results in multiple levels of inhibition