Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJLNAW)

• DTT Name: Tissue kallikrein (KLK2)
• Synonyms: hGK-1; Tissue kallikrein-2; Kallikrein-2; Glandular kallikrein-1
• Gene Name: KLK2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: KLK2_HUMAN
• TTD ID: T01908
• EC Number: EC 3.4.21.35
• Sequence:
  MWDLVLSIALSVGCTGAVPLIQSRIVGGWECEKHSQPWQVAVYSHGWAHCGGVLVHPQWV
  LTAAHCLKKNSQVWLGRHNLFEPEDTGQRVPVSHSFPHPLYNMSLLKHQSLRPDEDSSHD
  LMLLRLSEPAKITDVVKVLGLPTQEPALGTTCYASGWGSIEPEEFLRPRSLQCVSLHLLS
  NDMCARAYSEKVTEFMLCAGLWTGGKDTCGGDSGGPLVCNGVLQGITSWGPEPCALPEKP
  AVYTKVVHYRKWIKDTIAANP
• Function: Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
• KEGG Pathway: Endocrine and other factor-regulated calcium reabsorption (hsa04961)
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avoralstat	DM5YHU2	Hereditary angioedema	4A00.14	Phase 2/3	[1]
VDA-1102	DMAJ85O	Actinic keratosis	EK90.0	Phase 2	[2]
JNJ-69086420	DM6VR13	Prostate cancer	2C82.0	Phase 1	[3]
JNJ-75229414	DMV6XBC	Prostate cancer	2C82.0	Phase 1	[4]
JNJ-78278343	DM27FAN	Prostate cancer	2C82.0	Phase 1	[5]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dermolastin	DM6WSU2	Atopic dermatitis	EA80	Discontinued in Phase 2	[6]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DM-107	DMRYQVJ	Atopic dermatitis	EA80	Investigative	[7]
hK2p01 derivative KLK2 inhibitor	DME13RQ	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Atopic dermatitis	EA90	Skin	2.30E-01	-0.02	-0.2

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of Vidac Pharma.
• [3] ClinicalTrials.gov (NCT04644770) A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer. U.S. National Institutes of Health.
• [4] ClinicalTrials.gov (NCT05022849) A Phase 1, Dose Escalation Study of JNJ-75229414, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against KLK2 for Metastatic Castration-Resistant Prostate Cancer. U.S.National Institutes of Health.
• [5] ClinicalTrials.gov (NCT04898634) A Phase 1 Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer. U.S.National Institutes of Health.
• [6] Arriva-ProMetic recombinant alpha 1-antitrypsin (rAAT) moves into the clinic for dermatology applications. ProMetic Life Sciences. 2009.
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2372).
• [8] Novel peptide inhibitors of human kallikrein 2. J Biol Chem. 2006 May 5;281(18):12555-60.