Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Neurotrophic tyrosine kinase ROR1 (ROR1)
• Synonyms: receptor tyrosine kinase-like orphan receptor 1; receptor tyrosine kinase like orphan receptor 1; neurotrophic tyrosine kinase, receptor-related 1; dJ537F10.1; Tyrosine-protein kinase transmembrane receptor ROR1; NTRKR1; Inactive tyrosine-protein kinase transmembrane receptor ROR1
• Gene Name: ROR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: ROR1_HUMAN
• TTD ID: T87871
• Sequence:
  MHRPRRRGTRPPLLALLAALLLAARGAAAQETELSVSAELVPTSSWNISSELNKDSYLTL
  DEPMNNITTSLGQTAELHCKVSGNPPPTIRWFKNDAPVVQEPRRLSFRSTIYGSRLRIRN
  LDTTDTGYFQCVATNGKEVVSSTGVLFVKFGPPPTASPGYSDEYEEDGFCQPYRGIACAR
  FIGNRTVYMESLHMQGEIENQITAAFTMIGTSSHLSDKCSQFAIPSLCHYAFPYCDETSS
  VPKPRDLCRDECEILENVLCQTEYIFARSNPMILMRLKLPNCEDLPQPESPEAANCIRIG
  IPMADPINKNHKCYNSTGVDYRGTVSVTKSGRQCQPWNSQYPHTHTFTALRFPELNGGHS
  YCRNPGNQKEAPWCFTLDENFKSDLCDIPACDSKDSKEKNKMEILYILVPSVAIPLAIAL
  LFFFICVCRNNQKSSSAPVQRQPKHVRGQNVEMSMLNAYKPKSKAKELPLSAVRFMEELG
  ECAFGKIYKGHLYLPGMDHAQLVAIKTLKDYNNPQQWTEFQQEASLMAELHHPNIVCLLG
  AVTQEQPVCMLFEYINQGDLHEFLIMRSPHSDVGCSSDEDGTVKSSLDHGDFLHIAIQIA
  AGMEYLSSHFFVHKDLAARNILIGEQLHVKISDLGLSREIYSADYYRVQSKSLLPIRWMP
  PEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRQLLPCSEDCPPR
  MYSLMTECWNEIPSRRPRFKDIHVRLRSWEGLSSHTSSTTPSGGNATTQTTSLSASPVSN
  LSNPRYPNYMFPSQGITPQGQIAGFIGPPIPQNQRFIPINGYPIPPGYAAFPAAHYQPTG
  PPRVIQHCPPPKSRSPSSASGSTSTGHVTSLPSSGSNQEANIPLLPHMSIPNHPGGMGIT
  VFGNKSQKPYKIDSKQASLLGDANIHGHTESMISAEL
• Function: Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling. In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells. Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo.
• KEGG Pathway: Wnt signaling pathway (hsa04310)
• Reactome Pathway: WNT5A-dependent internalization of FZD2, FZD5 and ROR2 (R-HSA-5140745)

Molecular Interaction Atlas (MIA) of This DTT

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zilovertamab vedotin	DM1MZAQ	Diffuse large B-cell lymphoma	2A81	Phase 2/3	[2]
Cirmtuzumab	DM98RW0	Chronic lymphocytic leukaemia	2A82.0	Phase 2	[3]
VLS-101	DMLT94F	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
Zilovertamab	DMMEJ6K	Mantle cell lymphoma	2A85.5	Phase 2	[5]
NBE-002	DMTAODR	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[6]
ROR1 CAR-specific Autologous T-Lymphocytes	DM5EUIY	Acute lymphoblastic leukaemia	2A85	Phase 1	[1]
ROR1R-CAR-T Cell	DMIAK9P	leukaemia	2A60-2B33	Phase 1	[7]

References

• [1] ClinicalTrials.gov (NCT02706392) Genetically Modified T-Cell Therapy in Treating Patients With Advanced ROR1+ Malignancies
• [2] ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient-derived xenograft mouse models. Blood. 2021 Jun 17;137(24):3365-3377.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of VelosBio.
• [5] The Anti-ROR1 Monoclonal Antibody Zilovertamab Inhibits the Proliferation of Ovarian and Endometrial Cancer Cells. Pharmaceutics. 2022 Apr 11;14(4):837.
• [6] Clinical pipeline report, company report or official report of NBE-Therapeutics.
• [7] ClinicalTrials.gov (NCT02194374) Autologous ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL)