PMADS

Id:	acc3586
Group:	2sens
Protein:	MCL-1
Gene Symbol:	MCL1
Protein Id:	Q07820
Protein Name:	MCL1_HUMAN
PTM:	phosphorylation
Site:	Thr161
Site Sequence:	NNTSTDGSLPSTPPPAEEEED
Disease Category:	Cancer
Disease:	Leukemia
Disease Subtype:	Acute Myeloid Leukemia
Disease Cellline:
Disease Info:
Drug:	Venetoclax + Gilteritinib
Drug Info:	Venetoclax is a drug used in certain cancer treatments \| Gilteritinib is also a medication that plays a role in treating specific types of cancers.
Effect:	modulate
Effect Info:	Decreased phosphorylation of Thr161 weakens the stability of MCL-1 and enhances its tendency to degrade.
Note:
Score:	4.0
Pubmed(PMID):	35857899
Sentence Index:	35857899_10-11
Sentence:	"MCL-1 downregulation was associated with increased MCL-1 phosphorylation of serine 159, decreased phosphorylation of threonine 161 and proteasomal degradation. Gilteritinib and venetoclax were active in a FLT3 wildtype AML PDX model with TP53 mutation and reduced leukemic burden in four FLT3 wildtype AML patients receiving venetoclax-gilteritinib off-label after developing refractory disease under venetoclax-azacitidine."

Sequence & Structure:

MFGLKRNAVIGLNLYCGGAGLGAGSGGATRPGGRLLATEKEASARREIGGGEAGAVIGGSAGASPPSTLTPDSRRVARPPPIGAEVPDVTATPARLLFFAPTRRAAPLEEMEAPAADAIMSPEEELDGYEPEPLGKRPAVLPLLELVGESGNNTSTDGSLPSTPPPAEEEEDELYRQSLEIISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDWLVKQRGWDGFVEFFHVEDLEGGIRNVLLAFAGVAGVGAGLAYLIR

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	3	Withdrawn	small cell lung carcinoma	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	3	Withdrawn	small cell lung carcinoma	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	Hodgkins lymphoma	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	Hodgkins lymphoma	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	myelodysplastic syndrome	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	acute myeloid leukemia	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	myelodysplastic syndrome	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	follicular lymphoma	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	follicular lymphoma	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	myelofibrosis	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	2	Completed	myelofibrosis	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Completed	chronic lymphocytic leukemia	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Completed	chronic lymphocytic leukemia	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	diffuse large B-cell lymphoma	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	diffuse large B-cell lymphoma	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Completed	small cell lung carcinoma	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Completed	small cell lung carcinoma	ClinicalTrials ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	multiple myeloma	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	multiple myeloma	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Completed	lymphoid neoplasm	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Completed	lymphoid neoplasm	ClinicalTrials
MCL1	OBATOCLAX	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	metastatic melanoma	ClinicalTrials
MCL1	OBATOCLAX MESYLATE	Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitor	1	Terminated	metastatic melanoma	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

MCL1-Ser121
Cancer	Intensity
BRCA	1.735
COAD	-0.363
HGSC
ccRCC	-0.848
GBM
HNSC
LUAD	-0.245
LUSC	-0.279
non_ccRCC
PDAC
UCEC

MCL1-Ser150
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.363
GBM	1.584
HNSC	0.338
LUAD	-0.901
LUSC
non_ccRCC
PDAC
UCEC	-0.658

MCL1-Ser159
Cancer	Intensity
BRCA
COAD	-0.489
HGSC
ccRCC	-1.174
GBM
HNSC	0.807
LUAD	0.856
LUSC
non_ccRCC
PDAC
UCEC

MCL1-Ser162
Cancer	Intensity
BRCA
COAD	-1.323
HGSC	-0.231
ccRCC	-0.964
GBM	1.077
HNSC	0.909
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.532

MCL1-Ser60
Cancer	Intensity
BRCA
COAD
HGSC	-1.244
ccRCC	-0.375
GBM
HNSC	0.132
LUAD	-0.028
LUSC
non_ccRCC
PDAC
UCEC	1.515

MCL1-Ser64
Cancer	Intensity
BRCA	0.434
COAD
HGSC	-2.572
ccRCC	0.115
GBM	0.309
HNSC	0.671
LUAD	0.439
LUSC	0.663
non_ccRCC	-0.059
PDAC
UCEC	0

MCL1-Thr163
Cancer	Intensity
BRCA
COAD	-1.014
HGSC	0.029
ccRCC
GBM	0.985
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

No data.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb