Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT98BIB)

• DOT Name: PAK4-inhibitor INKA1 (INKA1)
• Synonyms: Induced in neural crest by AP2-alpha protein homolog; Inca; Inka-box actin regulator 1
• Gene Name: INKA1
• Related Disease: Acute undifferentiated leukemia
• UniProt ID: INKA1_HUMAN
• PDB ID: 4XBR; 4XBU
• Pfam ID: PF15342
• Sequence:
  MDMHSARLDSFLSQLRWELLCGRDTGSPSMPGPLQPTSQTGPDVQPSHQLRASGALEEDS
  VCCVEEEEEEEEEAVVTEDRDAALGGPREHALDWDSGFSEVSGSTWREEELPVSQRPAPS
  AQPLRRQCLSVSGLPMPSRAPVASVPPVHHPRPKSTPDACLEHWQGLEAEDWTAALLNRG
  RSRQPLVLGDNCFADLVHNWMELPETGSEGGDGGGHRARARPPQFLLGLSEQLRRRLARA
  RRTAMAGKRLSCPPRPEPELPADVSRFAALMSCRSRQPIICNDVSYL
• Function: Inhibitor of the serine/threonine-protein kinase PAK4. Acts by binding PAK4 in a substrate-like manner, inhibiting the protein kinase activity.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of PAK4-inhibitor INKA1 (INKA1).	[2]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of PAK4-inhibitor INKA1 (INKA1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of PAK4-inhibitor INKA1 (INKA1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of PAK4-inhibitor INKA1 (INKA1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PAK4-inhibitor INKA1 (INKA1).	[6]

References

• [1] A stemness screen reveals C3orf54/INKA1 as a promoter of human leukemia stem cell latency.Blood. 2019 May 16;133(20):2198-2211. doi: 10.1182/blood-2018-10-881441. Epub 2019 Feb 22.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.