Table 1 Drugs targeting metabolic activities in myeloid leukemia

Hexokinases

Glycolysis

2-Deoxyglucose

AML

[10]

-

AML with FTL3-ITD mutation

[23,24,25]

-

mTOR kinase

mTOR-dependent metabolic pathways

Sirolimus (rapamycin), temsirolimus, everolimus

AML/ CML

[19,20,21,22]

Phase I/II

Glutaminase

Glutaminolysis

CB839

AML

[26, 27]

Phase I

AML with IDH mutations

[28]

-

Asparagine glutamine availability

Amino acid metabolism

Erwinase alone L-asparaginase (encapsulated in red blood cells) + low-dose cytarabine

AML

Phase I/II

Arginine availability

Nucleotides polyamines biosynthesis

ADI-PEG20

AML

[29]

Phase I/II [30]

CKMT1

Creatine biosynthesis and OxPHOS

Cyclocreatine

AML with EVI1 aberrant expression

[31]

-

Mitochondrial protein translation

OxPHOS

Tigecycline

AML

[32]

Phase I

Mitochondrial protease ClpP

OxPHOS

A2-32-01

AML

[33]

-

mtDNA polymerase

OxPHOS

2'3'-Dideoxycytidine

AML

[34]

-

ETC complex I

OxPHOS

Metformin

AML

[35, 36]

Phase I

IACS-010759

AML

[37]

Phase I

DHODH

Nucleotides and OxPHOS

Brequinar sodium BRQ

AML

[38]

Phase I/II

HZ00

CML

[39]

-

Isobavalchone

AML

[40]

-

PTC299

AML

[41]

Phase Ib

CPT1a

Fatty acid oxidation

Etomoxir

AML

[42, 43]

-

Avocatin B

[44, 45]

-

ST1326

[46]

-

Mitochondrial anti-apoptotic BCL2

OxPHOS and pyrimidine biosynthesis

Venetoclax ABT-199

AML/ CML

[47,48,49]

Phase I/II/III [50]

AML with FTL3-ITD mutation

[51]

Phase I/II in combination with FLT3-ITD inhibitor

AML with IDH1 mutation

[52]

Phase I/II in combination with IDH1 mutant inhibitor

Amino acid transporters

AA metabolism and OxPHOS

Venetoclax ABT-199 + azacitidine

AML

[48]

Phase I/II/III [50]

IDH2 mutant enzyme

2-HG production

Enasidenib AG-221

AML with IDH2 mutation

[53,54,55]

FDA approved phase I/III

IDH1 mutant enzyme

2-HG production

Ivosidenib AG-120

AML with IDH1 mutation

[56, 57]

FDA approved phase I/III

BAY1436032

[58,59,60]

Phase I

IDH305

Phase I [61]

IDH1/IDH2 mutant enzyme

2-HG production

Vorasidenib AG-881

AML with IDH1 and/or IDH2 mutation

Phase I [62]

HMG-CoA reductase

Mevalonate biosynthesis

Statins: lovastatin, pravastatin

AML

[63,64,65]

Phase I/II [66, 67]

Stearoyl CoA desaturase 1

Lipid biosynthesis

BaP = combination of lipid-regulating bezafibrate and the sex hormone medroxyprogesterone acetate

AML

[68,69,70]

-