MELK

Summary

MELK (maternal embryonic leucine zipper kinase, HGNC:16870) is a protein-coding gene on chromosome 9p13.2, encoding Maternal embryonic leucine zipper kinase (Q14680). Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation.

Enables calcium ion binding activity; non-membrane spanning protein tyrosine kinase activity; and protein serine/threonine kinase activity. Involved in apoptotic process; cell population proliferation; and protein autophosphorylation. Located in cell cortex and plasma membrane.

Source: NCBI Gene 9833 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 127 total
• Druggable target: yes — 44 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014791

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16870
Approved symbol	MELK
Name	maternal embryonic leucine zipper kinase
Location	9p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0175
Ensembl gene	ENSG00000165304
Ensembl biotype	protein_coding
OMIM	607025
Entrez	9833

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 37 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000298048, ENST00000480021, ENST00000487398, ENST00000489766, ENST00000495529, ENST00000536329, ENST00000536860, ENST00000536987, ENST00000541717, ENST00000543751, ENST00000545008, ENST00000625974, ENST00000626154, ENST00000627766, ENST00000855345, ENST00000855346, ENST00000855347, ENST00000855348, ENST00000855349, ENST00000855350, ENST00000855351, ENST00000855352, ENST00000855353, ENST00000920555, ENST00000920556, ENST00000920557, ENST00000920558, ENST00000920559, ENST00000920561, ENST00000920562, ENST00000920565, ENST00000920568, ENST00000920570, ENST00000920572, ENST00000920574, ENST00000920575, ENST00000920576, ENST00000920577, ENST00000920578, ENST00000944510, ENST00000944511, ENST00000944512, ENST00000944513

RefSeq mRNA: 9 — MANE Select: NM_014791 NM_001256685, NM_001256687, NM_001256688, NM_001256689, NM_001256690, NM_001256691, NM_001256692, NM_001256693, NM_014791

CCDS: CCDS59123, CCDS59124, CCDS59125, CCDS59126, CCDS59127, CCDS59128, CCDS6606

Canonical transcript exons

ENST00000298048 — 18 exons

Exon	Start	End
ENSE00000700398	36665350	36665581
ENSE00000700445	36669310	36669406
ENSE00000700463	36670998	36671166
ENSE00000833110	36642997	36643083
ENSE00000833111	36651746	36651877
ENSE00000833112	36657241	36657363
ENSE00000982387	36674834	36674937
ENSE00002244662	36677160	36677682
ENSE00003467490	36581644	36581739
ENSE00003492577	36633102	36633200
ENSE00003494782	36607575	36607673
ENSE00003588703	36597222	36597290
ENSE00003598235	36599394	36599486
ENSE00003613759	36583627	36583712
ENSE00003615095	36589536	36589652
ENSE00003619946	36630299	36630367
ENSE00003679367	36594628	36594771
ENSE00003767675	36572895	36573007

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7434 / max 332.3969, expressed in 1554 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96684	18.1119	1551
96685	0.3760	207
96686	0.2556	164

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.89	gold quality
oocyte	CL:0000023	99.71	gold quality
ventricular zone	UBERON:0003053	94.49	gold quality
esophagus squamous epithelium	UBERON:0006920	92.65	gold quality
embryo	UBERON:0000922	91.82	gold quality
squamous epithelium	UBERON:0006914	90.09	gold quality
ganglionic eminence	UBERON:0004023	89.42	gold quality
epithelium of esophagus	UBERON:0001976	89.39	gold quality
amniotic fluid	UBERON:0000173	89.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.02	gold quality
tongue squamous epithelium	UBERON:0006919	88.81	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.57	gold quality
cervix squamous epithelium	UBERON:0006922	86.12	silver quality
gingival epithelium	UBERON:0001949	85.60	silver quality
tibia	UBERON:0000979	85.24	gold quality
trabecular bone tissue	UBERON:0002483	84.08	gold quality
gingiva	UBERON:0001828	83.25	silver quality
bone marrow	UBERON:0002371	82.89	gold quality
oral cavity	UBERON:0000167	82.64	gold quality
stromal cell of endometrium	CL:0002255	82.02	gold quality
cervix epithelium	UBERON:0004801	81.84	silver quality
mucosa of sigmoid colon	UBERON:0004993	81.43	gold quality
mucosa of transverse colon	UBERON:0004991	80.88	gold quality
cartilage tissue	UBERON:0002418	80.74	gold quality
colonic mucosa	UBERON:0000317	80.72	gold quality
epithelium of nasopharynx	UBERON:0001951	80.70	silver quality
nasopharynx	UBERON:0001728	80.68	silver quality
rectum	UBERON:0001052	80.43	gold quality
sperm	CL:0000019	79.97	silver quality
male germ cell	CL:0000015	79.62	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	345.23
E-MTAB-7052	yes	247.44
E-ANND-3	yes	5.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting MELK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-466	99.67	70.85	2863

Literature-anchored findings (GeneRIF, showing 40)

• pEg3 is a potential regulator of the G2/M progression and may act antagonistically to the CDC25B phosphatase,pEg3 kinase is able to specifically phosphorylate CDC25B in vitro. One phosphorylation site was identified and corresponded to serine 323 (PMID:12400006)
• analysis of MELK substrate specificity and activity regulation (PMID:16216881)
• the kinase activity of MELK is likely to affect mammary carcinogenesis through inhibition of the pro-apoptotic function of Bcl-GL (PMID:17280616)
• a critical role for MELK in the proliferation of brain tumors, including their stem cells, and suggest that MELK may be a compelling molecular target for treatment of high-grade brain tumors. (PMID:17722061)
• Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in astrocytomas (PMID:17960622)
• MELK expression is increased in breast cancer tissue and this is associated with poor survival. The most important factors controlling Bcl-G activity are post-translational modification by Fau & MELK. (PMID:19671159)
• High MELK is associated with brain tumor. (PMID:21558073)
• MELK could be associated with increased resistance of colorectal cancer cells against radiation and 5-FU. (PMID:21806965)
• MELK is upregulated in high-grade prostate cancer (PMID:22945237)
• Report MELK inhibitor that suppresses the growth of a wide range of human tumor cell lines. (PMID:23283305)
• Data indicate that expression-based risk indices of three genes UBE2C, TPX2, and MELK were more strongly associated with poor 5-year survival in adenocarcinoma patients. (PMID:23357462)
• The structural and biochemical analyses unravel the molecular mechanisms for the autophosphorylation/activation of MELK and the dependence of its catalytic activity on reducing agents. (PMID:23922895)
• our current knowledge of MELK function and recent discoveries in MELK signaling pathway were discussed. (PMID:24185907)
• advanced cancers with OTSSP167 started in 2013, as the first-in-class MELK inhibitor. This review summarizes the current molecular understanding of MELK and the recent preclinical studies about MELK as a cancer therapeutic target. (PMID:24795222)
• Together, these data indicate that MELK is a normally non-essential kinase, but is critical for basal-like breast cancer. (PMID:24844244)
• MELK promotes cell migration and invasion via the FAK/Paxillin pathway, and plays an important role in the occurrence and development of gastric cancer. (PMID:24885567)
• insight has been brought by the discovery of a protein complex of FOXM1 with the mitotic kinase MELK in cancer stem cells in brain cancers, as this protein complex appears to be cancer-specific (PMID:25017123)
• we report characterization of possible roles of MELK in acute myeloid leukemia (PMID:25365263)
• EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner (PMID:25601206)
• targeting MELK by the inhibition of both its catalytic activity and its protein stability might sensitize tumours to DNA-damaging agents or radiation therapy by lowering the DNA-damage threshold (PMID:26431963)
• Inhibition of MELK (genetically and pharmacologically) induces radiation sensitivity. (PMID:27225691)
• Synthesis of MCL1, an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B signaling. (PMID:27528663)
• MELK is an oncogenic kinase involved in the pathogenesis and recurrence of hepatocellular carcinoma. (PMID:27693640)
• MELK expression in hepatocellular carcinoma is extremely intense compared to its expression reported in other types of cancer and could be a promising effective tumor marker of HCC. (PMID:27798878)
• Report IL11RA and MELK amplification in gastric cancer cell lines and primary gastric adenocarcinomas. (PMID:27920471)
• Inhibition or depletion of MELK reduced cell proliferation and anchorage-dependent and -independent growth in various ovarian cancer cell lines through a G2/M cell cycle arrest, eventually resulting in apoptosis. (PMID:28214016)
• MELK-inhibitor has a role in triple-negative breast cancer cells demonstrating context-dependent response with p53 as a key determinant (PMID:28235006)
• Here, the authors report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types. Cells that harbor null mutations in MELK exhibit wild-type doubling times, cytokinesis, and anchorage-independent growth. (PMID:28337968)
• Study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness. (PMID:28536141)
• MELK is a host factor required for optimal uncoating of the HIV-1 core to promote viral cDNA synthesis. (PMID:28683086)
• In common culture conditions, the authors found that small molecule inhibition, genetic deletion, or acute depletion of MELK did not significantly affect cellular growth. (PMID:28926338)
• Here, the authors generate several additional knockout clones of MELK and demonstrate that across cancer types, cells lacking MELK exhibit wild-type growth in vitro, under environmental stress, in the presence of cytotoxic chemotherapies, and in vivo. (PMID:29417930)
• Study found that STRAP and MELK were overexpressed and highly phosphorylated in samples form colorectal adenocarcinoma patients and their expression were significantly correlated with tumor stages. (PMID:29783958)
• data suggest that MELK is a modulator of tumor cell growth and survival in a hypoxic microenvironment in adrenal cancer cells and support future investigation of its role as a therapeutic kinase target in patients with Adrenocortical Carcinoma. (PMID:29790920)
• MELK is highly expressed in cervical cancer and correlates with tumor metastasis. MELK is positively involved in cervical cancer cell proliferation, apoptosis, colony formation, and DNA damage repair. Therefore, MELK may be a novel biomarker predicting the poor prognosis of cervical cancer. (PMID:30334367)
• our results indicate that MELK indirectly mediates efficient processing of replication-associated DNA lesions in neuroblastoma, and that OTS167 sensitizes cells to DNA-damaging agents by abrogating this process. Further studies evaluating the activity of combination treatment regimens with OTS167 in neuroblastoma are warranted. (PMID:30674566)
• These findings uncover an important role of MELK and USP36 in mediating EZH2 stability in extranodal natural killer/T-cell lymphoma (NKTL). Moreover, MELK overexpression led to decreased sensitivity to bortezomib treatment in NKTL based on deprivation of EZH2 ubiquitination. (PMID:31434700)
• MELK is a poor biomarker for non-small-cell lung carcinoma patients (PMID:31599664)
• MELK is Upregulated in Advanced Clear Cell Renal Cell Carcinoma and Promotes Disease Progression by Phosphorylating PRAS40. (PMID:31813279)
• We analyzed the expression of MELK and two putative targets, Forkhead Box M1 (FOXM1) and Enhancer of Zeste Homolog 2 (EZH2), in a collection of human iCCA by real-time RT-PCR and immunohistochemistry (IHC). The effects on iCCA growth of both the multi-kinase inhibitor OTSSP167 and specific small-interfering RNA (siRNA) against MELK were investigated in iCCA cell lines. (PMID:31861475)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	melk	ENSDARG00000030759
mus_musculus	Melk	ENSMUSG00000035683
rattus_norvegicus	Melk	ENSRNOG00000013598
caenorhabditis_elegans		WBGENE00021012

Paralogs (17): NUAK1 (ENSG00000074590), PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), HUNK (ENSG00000142149), SIK1 (ENSG00000142178), BRSK1 (ENSG00000160469), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), NUAK2 (ENSG00000163545), SNRK (ENSG00000163788), SIK2 (ENSG00000170145), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203), TSSK1B (ENSG00000212122)

Protein

Protein identifiers

Maternal embryonic leucine zipper kinase — Q14680 (reviewed: Q14680)

Alternative names: Protein kinase Eg3, Protein kinase PK38, Tyrosine-protein kinase MELK

All UniProt accessions (5): A0A0D9SFB9, A0A0D9SFF9, A0A0D9SFL8, A0A0D9SGI4, Q14680

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.

Subunit / interactions. Monomer. Interacts with ZNF622 and PPP1R8.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in placenta, kidney, thymus, testis, ovary and intestine.

Post-translational modifications. Autophosphorylated: autophosphorylation of the T-loop at Thr-167 and Ser-171 is required for activation. Thr-478 phosphorylation during mitosis promotes interaction with PPP1R8.

Disease relevance. Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.

Activity regulation. Activated by autophosphorylation of the T-loop at Thr-167 and Ser-171: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-167 is not mediated by STK11/LKB1 but via autophosphorylation instead. Inhibited by calcium-binding. Kinase activity is also regulated by reducing agents: dithiothreitol (DTT) or reduced glutathione are required for kinase activity in vitro; such dependence is however not due to the presence of disulfide bonds.

Domain organisation. The KA1 domain mediates binding to phospholipids and targeting to membranes.

Induction. Up-regulated in many cancers cells. Up-regulated upon treatment with radiation or 5-fluorouracil (5-FU) in colorectal cancer cells, suggesting that it might be associated with increased resistance of colorectal cells against radiation and 5-FU. Down-regulated upon siomycin A, a thiazole antibiotic, treatment, leading to inhibit tumor growth in vivo.

Miscellaneous. Potential therapeutic target for treatment of somatic tumors, such as brain and breast cancers, down-regulation of MELK inhibiting tumorigenesis.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Isoforms (8)

UniProt ID	Names	Canonical?
Q14680-1	1	yes
Q14680-2	2
Q14680-3	3
Q14680-4	4
Q14680-5	5
Q14680-6	6
Q14680-7	7
Q14680-8	8

RefSeq proteins (9): NP_001243614, NP_001243616, NP_001243617, NP_001243618, NP_001243619, NP_001243620, NP_001243621, NP_001243622, NP_055606* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001772	KA1_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR028375	KA1/Ssp2_C	Homologous_superfamily
IPR034673	MELK	Domain
IPR048637	MELK_UBA	Domain

Pfam: PF00069, PF02149, PF21594

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (106 total): mutagenesis site 26, modified residue 22, helix 18, strand 12, splice variant 7, sequence variant 5, sequence conflict 5, turn 3, domain 2, region of interest 2, binding site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5K00	X-RAY DIFFRACTION	1.77
5IH9	X-RAY DIFFRACTION	1.79
4BKY	X-RAY DIFFRACTION	1.83
5IH8	X-RAY DIFFRACTION	1.85
5M5A	X-RAY DIFFRACTION	1.9
4D2W	X-RAY DIFFRACTION	1.92
5IHA	X-RAY DIFFRACTION	1.96
4UMT	X-RAY DIFFRACTION	1.98
5MAH	X-RAY DIFFRACTION	2
9F31	X-RAY DIFFRACTION	2
4UMU	X-RAY DIFFRACTION	2.02
6VXR	X-RAY DIFFRACTION	2.1
5IHC	X-RAY DIFFRACTION	2.14
5MAI	X-RAY DIFFRACTION	2.15
4BKZ	X-RAY DIFFRACTION	2.2
6GVX	X-RAY DIFFRACTION	2.24
5TVT	X-RAY DIFFRACTION	2.28
4UMP	X-RAY DIFFRACTION	2.3
5MAG	X-RAY DIFFRACTION	2.35
5TWL	X-RAY DIFFRACTION	2.42
4D2V	X-RAY DIFFRACTION	2.45
4D2P	X-RAY DIFFRACTION	2.55
4BL1	X-RAY DIFFRACTION	2.6
4UMQ	X-RAY DIFFRACTION	2.6
5TWU	X-RAY DIFFRACTION	2.6
5TWZ	X-RAY DIFFRACTION	2.63
4D2T	X-RAY DIFFRACTION	2.7
4IXP	X-RAY DIFFRACTION	2.75
5MAF	X-RAY DIFFRACTION	2.8
5TX3	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14680-F1	70.35	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 132 (proton acceptor)

Ligand- & substrate-binding residues (2): 17–25; 40

Post-translational modifications (22): 167, 171, 253, 336, 343, 356, 367, 391, 398, 407, 409, 431, 478, 494, 498, 505, 518, 529, 529, 539 …

Mutagenesis-validated functional residues (26):

Position	Phenotype
29	abolishes dependence to reducing agents; when associated with v-70; a-89; a-154; a-168; a-169; a-204; a-286 and a-339.
70	abolishes dependence to reducing agents; when associated with v-29; a-89; a-154; a-168; a-169; a-204; a-286 and a-339.
89	abolishes dependence to reducing agents; when associated with v-29; v-70; a-154; a-168; a-169; a-204; a-286 and a-339.
150	abolishes enzymatic activity.
154	abolishes dependence to reducing agents; when associated with v-29; v-70; a-89; a-168; a-169; a-204; a-286 and a-339.
163	abolishes autophosphorylation on tyrosine but still active on exogenous substrates.
167	abolishes activation of serine/threonine-protein kinase activity and has only weak activity.
167	phosphomimetic mutant that has similar kinase activity as wild-type.
168	abolishes dependence to reducing agents; when associated with v-29; v-70; a-89; a-154; a-169; a-204; a-286 and a-339.
169	abolishes dependence to reducing agents; when associated with v-29; v-70; a-89; a-154; a-168; a-204; a-286 and a-339.
171	abolishes activation of serine/threonine-protein kinase activity and has only weak activity.
171	inactive.
204	abolishes dependence to reducing agents; when associated with v-29; v-70; a-89; a-154; a-168; a-169; a-286 and a-339.
283–285	inactive.
286	abolishes dependence to reducing agents; when associated with v-29; v-70; a-89; a-154; a-168; a-169; a-204; and a-339.
339	abolishes dependence to reducing agents; when associated with v-29; v-70; a-89; a-154; a-168; a-169; a-204 and a-286.
345	no effect on interaction with ppp1r8.
387	no effect on interaction with ppp1r8.
409	no effect on interaction with ppp1r8.
415	no effect on interaction with ppp1r8.
428	no effect on interaction with ppp1r8.
446	inhibits interaction with ppp1r8.
460	inhibits interaction with ppp1r8.
466	inhibits interaction with ppp1r8.
478	strongly inhibits interaction with ppp1r8. enhances enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 311 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GNF2_CKS1B, E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, MODULE_451, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, MITSIADES_RESPONSE_TO_APLIDIN_DN, KONG_E2F3_TARGETS, GNF2_RRM2, HATADA_METHYLATED_IN_LUNG_CANCER_DN, GNF2_RRM1, SHEPARD_BMYB_MORPHOLINO_DN, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (9): G2/M transition of mitotic cell cycle (GO:0000086), apoptotic process (GO:0006915), cell population proliferation (GO:0008283), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), hemopoiesis (GO:0030097), positive regulation of apoptotic process (GO:0043065), protein autophosphorylation (GO:0046777), neural precursor cell proliferation (GO:0061351), protein phosphorylation (GO:0006468)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), non-membrane spanning protein tyrosine kinase activity (GO:0004715), calcium ion binding (GO:0005509), ATP binding (GO:0005524), lipid binding (GO:0008289), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): plasma membrane (GO:0005886), cell cortex (GO:0005938), membrane (GO:0016020), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
binding	2
cell periphery	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
intrinsic apoptotic signaling pathway	1
cell development	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
protein phosphorylation	1
cell population proliferation	1
phosphorylation	1
protein modification process	1
protein tyrosine kinase activity	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
membrane	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2807 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MELK	ZNF622	Q969S3	958
MELK	FOXM1	Q08050	875
MELK	CCNB2	O95067	823
MELK	DLGAP5	Q15398	813
MELK	CCNB1	P14635	809
MELK	MYBL2	P10244	806
MELK	BUB1	O43683	759
MELK	CEP55	Q53EZ4	751
MELK	KIF4A	O95239	750
MELK	TOP2A	P11388	740
MELK	TPX2	Q9ULW0	740
MELK	UBE2C	O00762	719
MELK	ASPM	Q8IZT6	715
MELK	BIRC5	O15392	697
MELK	BUB1B	O60566	684

IntAct

130 interactions, top by confidence:

A	B	Type	Score
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
MELK	BCL2L14	psi-mi:“MI:0915”(physical association)	0.650
BCL2L14	MELK	psi-mi:“MI:0915”(physical association)	0.650
MELK	BCL2L14	psi-mi:“MI:0407”(direct interaction)	0.650
BCL2L14	MELK	psi-mi:“MI:0217”(phosphorylation reaction)	0.650
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MELK	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
	SGK1	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
P4HA2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
ZNG1A	AGAP1	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350

BioGRID (149): MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS), MELK (Affinity Capture-MS)

ESM2 similar proteins: A6NAF9, A6QLE1, A9CPT4, B4F7C4, D2H0H6, D2H3M0, E1BPH3, E1C3S7, E2QTD3, E2RDV1, E7FDW8, F1R237, Q14596, Q14680, Q149N8, Q1L981, Q1RMU2, Q4R3G4, Q587J7, Q58EK5, Q5DTW2, Q5JPI3, Q5M7P8, Q5RAH6, Q5RCV3, Q5RED8, Q5VCS6, Q5VUG0, Q5VZ19, Q66H62, Q6NU04, Q6ZMV9, Q7TPQ3, Q80TQ2, Q8IZC4, Q8IZE3, Q8K1H1, Q8NAT2, Q8NE18, Q8NHU6

Diamond homologs: A0A2I0BVG8, A0A509AFG4, A0A509AHB6, A0A509ALV6, A0A509AQE6, A0A5K1K8H0, A2XFF4, A8X6H4, B8BBT7, E9PT87, F4JBP3, O15865, O22932, O61267, O70150, O80673, P05986, P08414, P13234, P18654, P22216, P22517, P25323, P27466, P28582, P34101, P40376, P51812, P53681, P53684, P62343, P62344, P62345, P92958, P93759, Q00771, Q09170, Q0D715, Q0VD22, Q10KY3

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
MELK	up-regulates	CDC25B	phosphorylation
MELK	up-regulates	MELK	phosphorylation
STK11	up-regulates	MELK	phosphorylation
MELK	“down-regulates activity”	CDC25B	phosphorylation
MELK	“down-regulates activity”	PDPK1	phosphorylation
MELK	“up-regulates quantity by stabilization”	EZH2	phosphorylation
MELK	“up-regulates activity”	FOXM1	phosphorylation
MELK	“up-regulates activity”	PTK2	phosphorylation
MELK	“down-regulates quantity”	FOXO3	phosphorylation
MELK	“down-regulates quantity”	FOXO1	phosphorylation
MELK	“up-regulates activity”	SQSTM1	phosphorylation
MELK	“up-regulates activity”	MAP3K5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	6	51.9×	2e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	45.8×	2e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	45.8×	2e-07
Activation of BH3-only proteins	6	33.9×	2e-06
RHO GTPases activate PKNs	6	21.6×	2e-05
Intrinsic Pathway for Apoptosis	6	20.0×	2e-05
G2/M Checkpoints	10	15.3×	2e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	14.0×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	17.7×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

127 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	9
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3126 predictions. Top by Δscore:

Variant	Effect	Δscore
9:36589534:A:AG	acceptor_gain	1.0000
9:36589534:AGAGT:A	acceptor_gain	1.0000
9:36589535:G:GG	acceptor_gain	1.0000
9:36589535:GA:G	acceptor_gain	1.0000
9:36589535:GAGT:G	acceptor_gain	1.0000
9:36589535:GAGTG:G	acceptor_gain	1.0000
9:36594615:A:AG	acceptor_gain	1.0000
9:36594615:ATT:A	acceptor_gain	1.0000
9:36594616:T:G	acceptor_gain	1.0000
9:36594617:T:A	acceptor_gain	1.0000
9:36594620:T:A	acceptor_gain	1.0000
9:36594768:GCCA:G	donor_gain	1.0000
9:36594772:G:GG	donor_gain	1.0000
9:36597220:A:AG	acceptor_gain	1.0000
9:36597221:G:GG	acceptor_gain	1.0000
9:36597221:GGAAA:G	acceptor_gain	1.0000
9:36597291:G:GA	donor_loss	1.0000
9:36597292:T:TC	donor_loss	1.0000
9:36599386:A:AG	acceptor_gain	1.0000
9:36599388:T:A	acceptor_gain	1.0000
9:36599389:G:A	acceptor_gain	1.0000
9:36599392:A:AG	acceptor_gain	1.0000
9:36599392:AG:A	acceptor_gain	1.0000
9:36599393:G:GG	acceptor_gain	1.0000
9:36599393:GG:G	acceptor_gain	1.0000
9:36599393:GGGT:G	acceptor_gain	1.0000
9:36599484:GAG:G	donor_gain	1.0000
9:36599485:AGG:A	donor_loss	1.0000
9:36599487:G:GC	donor_loss	1.0000
9:36599487:G:GG	donor_gain	1.0000

AlphaMissense

4289 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:36594761:A:C	D132A	1.000
9:36607584:T:A	W193R	1.000
9:36607584:T:C	W193R	1.000
9:36583688:A:C	K40N	0.999
9:36583688:A:T	K40N	0.999
9:36594758:G:C	R131T	0.999
9:36594758:G:T	R131M	0.999
9:36594761:A:G	D132G	0.999
9:36594761:A:T	D132V	0.999
9:36594762:C:A	D132E	0.999
9:36594762:C:G	D132E	0.999
9:36594764:T:A	L133H	0.999
9:36594764:T:C	L133P	0.999
9:36594766:A:G	K134E	0.999
9:36594768:G:C	K134N	0.999
9:36594768:G:T	K134N	0.999
9:36597227:T:A	N137K	0.999
9:36597227:T:G	N137K	0.999
9:36597265:A:C	D150A	0.999
9:36597265:A:T	D150V	0.999
9:36597266:C:A	D150E	0.999
9:36597266:C:G	D150E	0.999
9:36599428:G:A	G170E	0.999
9:36599430:A:C	S171R	0.999
9:36599432:T:A	S171R	0.999
9:36599432:T:G	S171R	0.999
9:36607578:G:C	D191H	0.999
9:36607587:A:C	S194R	0.999
9:36607589:C:A	S194R	0.999
9:36607589:C:G	S194R	0.999

dbSNP variants (sampled 300 via entrez): RS1000016897 (9:36582620 T>C), RS1000030738 (9:36572192 T>C,G), RS1000035641 (9:36658857 A>G), RS1000053014 (9:36635323 G>A), RS1000112594 (9:36645892 C>T), RS1000129875 (9:36575414 A>G), RS1000172640 (9:36656524 C>A), RS1000177030 (9:36612271 GT>G), RS1000228914 (9:36641650 C>T), RS1000236284 (9:36583025 G>A), RS1000349789 (9:36582070 C>T), RS1000416280 (9:36622447 G>A), RS1000439259 (9:36576889 A>G), RS1000482478 (9:36607526 T>A,C), RS1000484911 (9:36649758 G>A)

Disease associations

OMIM: gene MIM:607025 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4578 (SINGLE PROTEIN), CHEMBL6066036 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

44 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 289,234 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL941	IMATINIB	4	111,611
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL38380	FASUDIL	3	11,953
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1614713	CC-401	2	389
CHEMBL1721885	SU-014813	2	363
CHEMBL1738758	ONVANSERTIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL2386889	SCH-900776	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL3218578	BGT-226 FREE BASE	2
CHEMBL402548	DANUSERTIB	2
CHEMBL495727	AT-9283	2
CHEMBL521851	PICTILISIB	2
CHEMBL564829	MILCICLIB	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — MELK subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
OTSSP167	Inhibition	9.39	pIC50
MELK-TI	Inhibition	7.64	pIC50
CC-401	Inhibition	6.47	pIC50

Binding affinities (BindingDB)

734 measured of 734 human assays (734 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US9067937, 2	IC50	0.3 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 44	IC50	0.3 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 61	IC50	0.4 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 28	IC50	0.4 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 202	IC50	0.46 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 4	IC50	0.5 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 15	IC50	0.5 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 71	IC50	0.5 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 81	IC50	0.5 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 48	IC50	0.6 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 70	IC50	0.6 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 80	IC50	0.6 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 89	IC50	0.6 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 94	IC50	0.6 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
(2S)-N-[4-[[3-acetyl-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl]amino]cyclohexyl]-2-aminopropanamide	IC50	0.66 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
US9067937, 9	IC50	0.7 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 27	IC50	0.7 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(3-hydroxypyrrolidin-1-yl)methyl]cyclohexyl]amino]quinolin-3-yl]methanone	IC50	0.73 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[[2-hydroxyethyl(methyl)amino]methyl]cyclohexyl]amino]quinolin-3-yl]methanone	IC50	0.74 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
[4-[[6-[(3R)-3-aminopiperidin-1-yl]-3-pyridinyl]amino]-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone	IC50	0.76 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
US9067937, 5	IC50	0.8 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 63	IC50	0.8 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
[6-(3-chloro-4-hydroxy-5-methoxyphenyl)-4-[4-[(dimethylamino)methyl]piperidin-1-yl]quinolin-3-yl]-cyclopropylmethanone	IC50	0.8 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[[2-hydroxyethyl(methyl)amino]methyl]cyclohexyl]amino]quinolin-3-yl]methanone	IC50	0.8 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]quinolin-3-yl]methanone	IC50	0.85 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
1-[4-[[6-(3-aminopiperidin-1-yl)-3-pyridinyl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]ethanone	IC50	0.86 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
US9067937, 14	IC50	0.9 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 62	IC50	0.9 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[1-(1-methylpyrrolidin-3-yl)pyrazol-4-yl]amino]quinolin-3-yl]ethanone	IC50	0.9 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
US9067937, 201	IC50	0.93 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
4-[4-[[6-(3-aminopiperidin-1-yl)-3-pyridinyl]amino]-3-methylsulfonylquinolin-6-yl]-2,6-dichlorophenol	IC50	0.94 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]quinolin-3-yl]ethanone	IC50	0.94 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
1-[4-[[6-(3-aminopiperidin-1-yl)-3-pyridinyl]amino]-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl]ethanone	IC50	0.99 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
US9067937, 12	IC50	1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 49	IC50	1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 75	IC50	1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 83	IC50	1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
[4-[[6-[(3R)-3-aminopiperidin-1-yl]-3-pyridinyl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone	IC50	1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
1-[6-(3-chloro-4-hydroxy-5-methoxyphenyl)-4-[[(1R,3R)-3-[(dimethylamino)methyl]cyclohexyl]amino]quinolin-3-yl]ethanone	IC50	1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
US9067937, 6	IC50	1.1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 93	IC50	1.1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
US9067937, 213	IC50	1.1 nM	US-9067937: 1,5-naphthyridine derivatives and MELK inhibitors containing the same
1-[4-[6-(3-chloro-4-hydroxy-5-methoxyphenyl)-3-(cyclopropanecarbonyl)quinolin-4-yl]piperazin-1-yl]-2-(dimethylamino)ethanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
[4-[4-(2-aminopropan-2-yl)anilino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
[4-[[2-(3-aminopiperidin-1-yl)pyrimidin-5-yl]amino]-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
[4-[[6-[(3S)-3-aminopiperidin-1-yl]-3-pyridinyl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]-4-hydroxycyclohexyl]amino]quinolin-3-yl]methanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
[4-[[1-(4-aminocyclohexyl)pyrazol-4-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]cyclohexyl]amino]quinolin-3-yl]ethanone	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same
2-(2,4-dioxo-3-phenyl-1,3-thiazolidin-5-yl)-N-naphthalen-1-ylacetamide	IC50	1.1 nM	US-9120749: Quinoline derivatives and MELK inhibitors containing the same

ChEMBL bioactivities

1217 potent at pChembl≥5 of 1226 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	IC50	0.15	nM	CHEMBL4077934
9.52	IC50	0.3	nM	CHEMBL3824328
9.52	IC50	0.3	nM	CHEMBL3688335
9.52	IC50	0.3	nM	CHEMBL3688376
9.50	Ki	0.3162	nM	CHEMBL1980995
9.41	Ki	0.39	nM	CHEMBL4062168
9.40	IC50	0.4	nM	CHEMBL3688339
9.40	IC50	0.4	nM	CHEMBL3692787
9.39	IC50	0.41	nM	CHEMBL3688339
9.34	IC50	0.46	nM	CHEMBL3692824
9.33	Ki	0.47	nM	CHEMBL1908392
9.30	IC50	0.5	nM	CHEMBL3688337
9.30	IC50	0.5	nM	CHEMBL3688348
9.30	IC50	0.5	nM	CHEMBL3692797
9.30	IC50	0.5	nM	CHEMBL3692807
9.27	IC50	0.542	nM	STAUROSPORINE
9.22	IC50	0.6	nM	CHEMBL3688380
9.22	IC50	0.6	nM	CHEMBL3692796
9.22	IC50	0.6	nM	CHEMBL3692806
9.22	IC50	0.6	nM	CHEMBL3692815
9.22	IC50	0.6	nM	CHEMBL3692820
9.18	IC50	0.66	nM	CHEMBL3684241
9.17	Ki	0.68	nM	CHEMBL4089284
9.16	IC50	0.687	nM	STAUROSPORINE
9.15	IC50	0.7	nM	CHEMBL3688342
9.15	IC50	0.7	nM	CHEMBL3688360
9.14	IC50	0.73	nM	CHEMBL3679230
9.13	IC50	0.74	nM	CHEMBL3679261
9.12	IC50	0.76	nM	CHEMBL3679276
9.10	IC50	0.8	nM	CHEMBL3688338
9.10	IC50	0.8	nM	CHEMBL3692789
9.10	IC50	0.8	nM	CHEMBL3674198
9.10	IC50	0.8	nM	CHEMBL3679261
9.07	IC50	0.86	nM	CHEMBL3679305
9.07	IC50	0.85	nM	CHEMBL3674217
9.05	IC50	0.9	nM	CHEMBL3688347
9.05	IC50	0.9	nM	CHEMBL3692788
9.05	IC50	0.9	nM	CHEMBL3684173
9.03	IC50	0.93	nM	CHEMBL3692823
9.03	IC50	0.94	nM	CHEMBL3684267
9.03	IC50	0.94	nM	CHEMBL3674238
9.00	IC50	1	nM	CHEMBL3823975
9.00	IC50	1	nM	CHEMBL3688345
9.00	IC50	1	nM	CHEMBL3688381
9.00	IC50	1	nM	CHEMBL3692801
9.00	IC50	1	nM	CHEMBL3692809
9.00	IC50	1	nM	CHEMBL3679275
9.00	IC50	0.99	nM	CHEMBL3679353
9.00	IC50	1	nM	CHEMBL3679369
9.00	Ki	1	nM	CHEMBL2005718

PubChem BioAssay actives

225 with measured affinity, of 1935 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[2-anilino-4-(piperidin-4-ylmethoxy)pyrimidin-5-yl]-N-[(6-methoxy-1H-benzimidazol-2-yl)methyl]benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0001	uM
4-[3-fluoro-4-[4-[3-(piperidin-4-ylmethoxy)-4-pyridinyl]pyrazol-1-yl]phenyl]morpholine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0003	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1415246: Inhibition of recombinant C-terminal His6-tagged human MELK expressed in Escherichia coli BL21 (DE3) RIL using FAM-GS-derived peptide as substrate after 3 hrs by IMAP method	ic50	0.0004	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylate	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0004	uM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0005	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531770: Inhibition of human MELK using KKLNRTLSFAEPG as substrate by [gamma-33P]-ATP assay	ic50	0.0005	uM
2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylic acid	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0007	uM
4-[[4-[1-[4-(4-methylpiperazin-1-yl)phenyl]pyrazol-4-yl]-3-pyridinyl]oxymethyl]cyclohexan-1-amine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0010	uM
4-[2-anilino-4-(piperidin-4-ylmethoxy)pyrimidin-5-yl]-N-(1H-benzimidazol-2-ylmethyl)benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0011	uM
N-[(6-methoxy-1H-benzimidazol-2-yl)methyl]-4-[4-(piperidin-4-ylmethoxy)-3-pyridinyl]benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0015	uM
N-[(6-methoxy-1H-benzimidazol-2-yl)methyl]-4-[2-(methylamino)-4-(piperidin-4-ylmethoxy)pyrimidin-5-yl]benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0015	uM
1-methyl-4-[4-[4-[3-(piperidin-4-ylmethoxy)-4-pyridinyl]pyrazol-1-yl]phenyl]piperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0020	uM
4-[5-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1779141: Inhibition of N-terminal GST-tagged MELK (1 to 493 residues) (unknown origin) expressed in Escherichia coli	ic50	0.0023	uM
2-hydroxy-N-methyl-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxamide	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0023	uM
N-[4-[[(5-fluoro-2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0031	uM
1-[4-[4-(3-cyclohexyloxy-4-pyridinyl)pyrazol-1-yl]phenyl]-4-methylpiperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0040	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625087: Binding constant for MELK kinase domain	kd	0.0049	uM
5-fluoro-3-[(3E)-3-(2-piperazin-1-ylethoxyimino)indol-2-yl]-1H-indol-2-ol;hydrochloride	1737406: Inhibition of human MELK in presence of ATP	ic50	0.0055	uM
1-methyl-4-[4-[4-(3-piperidin-4-yloxy-4-pyridinyl)pyrazol-1-yl]phenyl]piperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0060	uM
4-[4-[4-[3-(piperidin-4-ylmethoxy)-4-pyridinyl]pyrazol-1-yl]phenyl]morpholine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0060	uM
7-[3-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenoxy]prop-1-ynyl]isoquinoline	1177148: Inhibition of MELK (unknown origin) using KKLNRTLSFAEPG substrate by Millipore/scintillation counting analysis	ic50	0.0076	uM
2-hydroxy-N,N-dimethyl-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxamide	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0088	uM
N-(2-anilino-2-oxoethyl)-4-[2-anilino-4-(piperidin-4-ylmethoxy)pyrimidin-5-yl]benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0088	uM
1-methyl-4-[4-[4-[3-(2-methylpropoxy)-4-pyridinyl]pyrazol-1-yl]phenyl]piperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0090	uM
ethyl 4-[[4-(aminomethyl)cyclohexyl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridine-3-carboxylate	1650172: Binding affinity to wild-type human full length MELK (M1 to V651 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0090	uM
N-(1H-benzimidazol-2-ylmethyl)-4-[2-(methylamino)-4-(piperidin-4-ylmethoxy)pyrimidin-5-yl]benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0092	uM
ethyl 6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridine-3-carboxylate	1650172: Binding affinity to wild-type human full length MELK (M1 to V651 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0110	uM
N-(1H-benzimidazol-2-ylmethyl)-4-[4-(piperidin-4-ylmethoxy)-3-pyridinyl]benzamide	1439194: Inhibition of MELK (unknown origin) containing kinase domain and UBA domain using STK S1 as substrate after 20 mins by HTRF assay	ic50	0.0120	uM
N-butyl-6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridine-3-carboxamide	1650172: Binding affinity to wild-type human full length MELK (M1 to V651 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0120	uM
4-[1-(2-fluorophenyl)pyrazol-4-yl]-3-(piperidin-4-ylmethoxy)pyridine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0130	uM
ethyl 6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-(dimethylcarbamoyl)cyclohexyl]amino]-1,5-naphthyridine-3-carboxylate	1650172: Binding affinity to wild-type human full length MELK (M1 to V651 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0130	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148742: Binding affinity to human MELK incubated for 45 mins by Kinobead based pull down assay	kd	0.0155	uM
N-methyl-7-[3-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenoxy]prop-1-ynyl]isoquinolin-3-amine	1177148: Inhibition of MELK (unknown origin) using KKLNRTLSFAEPG substrate by Millipore/scintillation counting analysis	ic50	0.0190	uM
1-methyl-4-[4-[4-[3-(pyridin-4-ylmethoxy)-4-pyridinyl]pyrazol-1-yl]phenyl]piperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0250	uM
(Z)-2-cyano-3-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]prop-2-enamide	1928595: Inhibition of MELK (unknown origin)	ic50	0.0255	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507617: Binding affinity to MELK	kd	0.0260	uM
7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-2-[3-(pyrrolidin-1-ylmethyl)anilino]pyrrolo[2,3-d]pyrimidin-6-one	1992922: Inhibition of MELK (unknown origin)	ic50	0.0290	uM
4-(1-phenylpyrazol-4-yl)-3-(piperidin-4-ylmethoxy)pyridine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0360	uM
2-methoxy-4-(1H-pyrazol-4-yl)-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzamide	1177124: Inhibition of MELK kinase (unknown origin) using biotinylated ZIP-tide peptide/gamma[33P]ATP by scintillation counting analysis	ic50	0.0370	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526263: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MELK (unknown origin) (1 to 493 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0410	uM
N-[4-[[(5-acetyl-2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	1474637: Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0460	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526263: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MELK (unknown origin) (1 to 493 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0500	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1425074: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0570	uM
1-[4-[4-(3-methoxy-4-pyridinyl)pyrazol-1-yl]phenyl]-4-methylpiperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0640	uM
1-[4-[4-(3-fluoro-4-pyridinyl)pyrazol-1-yl]phenyl]-4-methylpiperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0700	uM
1-methyl-4-[4-(4-pyridin-4-ylpyrazol-1-yl)phenyl]piperazine	1311030: Inhibition of MELK catalytic domain (unknown origin) preincubated for 20 mins followed by addition of KinEASE STK S1 peptide as substrate in presence of 20 uM ATP measured after 20 mins by time-resolved fluorescence assay	ic50	0.0800	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	1425074: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0830	uM
(2,6-dimethyl-4-pyridinyl)-[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methanone	1779141: Inhibition of N-terminal GST-tagged MELK (1 to 493 residues) (unknown origin) expressed in Escherichia coli	ic50	0.0957	uM
4-amino-5-(5-bromothiophene-2-carbonyl)-2-(2-piperazin-1-ylethylamino)thiophene-3-carbonitrile	1536387: Inhibition of recombinant human MELK expressed in Escherichia coli using ZIPtide as substrate measured after 0.5 hrs by ADP-Glo assay	ic50	0.0980	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625087: Binding constant for MELK kinase domain	kd	0.0990	uM

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	4
sodium arsenite	increases expression, decreases expression, increases abundance	4
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	4
Estradiol	increases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Cisplatin	decreases expression, increases expression	2
Doxorubicin	decreases expression, affects cotreatment, affects response to substance	2
Fluorouracil	affects cotreatment, affects response to substance	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric oxide	decreases expression	1
isoliquiritigenin	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1

ChEMBL screening assays

392 unique, capped per target: 390 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003318	Binding	Inhibition of MELK at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1963804	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MELK	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1DT	Abcam HCT 116 MELK KO	Cancer cell line	Male
CVCL_SX78	HAP1 MELK (-)	Cancer cell line	Male

Clinical trials (associated diseases)

51 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
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