Table 1 Therapeutic targets

1

Proteolysis/alanine/transaminase/pyruvate

increased

aminooxacetic, 2PAM, D alanine,

β chloro-L-alanine

[42, 43]

2

Lactate dehydrogenase/pyruvate/lactate/NAD+

Malate dehydrogenase/OAA/malate/NAD+

Malic enzyme/malate/pyruvate/lactate/NAD+

increased

increased

increased

Br pyruvate, gossypol

D malate, humic acid

D malate

[44–46]

3

Glycolysis

increased

mannoheptulose, lodinamineepalresta, citrate

[47–49]

4

PEP carboxykinase/PEP/OAA

Pyruvate carboxylase/pyruvate/OAA

increased

decreased

Cl-PEP, β sulphopyruvate

3-hydroxybutyrate (ketone bodies will activate)

[50, 51]

[52]

5

Pyruvate kinase (M2 bottleneck)/PEP/pyruvate

Pyruvate dehydrogenase/pyruvate/acetylCoA

decreased

decreased

dihydroxyphenylethanol, polyethylene - glycol

lipoic acid, kinase inhibitors (dichloroacetate,

2-chloropropionate) or PP2A agonists (xylulose5P, B12, choline)

[53–55]

[16, 17]

6

Lipolytic fatty acid source of acetyl CoA

Carnitine transporter

increased

niacine, Growth hormone inhibitors

Avoid oxfenicine or levofloxacin

[56, 57]

7

Citrate synthase (OAA+ acetylCoA)/citrate

increased

Dserine, fluoroacetylCoA, carboxymethyl-CoA,

citrate (via product inhibition), capsaicine (via electron transport inhibition and NADH increase)

[13]

8

ATPcitrate lyase citrate/OAA+acetylCoA

Triglycerides synthesis via acetyl CoA

Other OAA sources

increased

increased

increased

hydroxycitrate, fluorocitrate

xanthohumol (removes triglycerides)

D malate

[58]

[59]

9

Choline dehydrogenase/methylation/lipotropic

Choline kinase/phosphorylcholine/lecithin

decreased

increased

choline

miltefosin, farnesol

[60, 61]

10

PP2A methylation (it counteracts signaling and enzyme kinases)

decreased

betaine, folate, B12, trimethylglycine (via SAM)

11

Histone deacetylase (gene silencing)

increased

butyrate, valproate, benzamide, trichostatin

[62]

12

Cytochrome P450 demethylase (hypomethylated promoters)HAT/hexokinase expression

Histone acetylase

increased

increased

ketonazole, bergamottin, quinine

anacardic acid, garcinol, curcumine

[63–67]

[66, 67]

13

Tyrosine kinase-signaling route (MAP kin, PI3 kin, PLCγ)

increased

imatinib mésilate (glivec chemotherapy)

14,15, 16

GH-IGF

IGFBP

increased

decreased

octreotide, pegvisomant

apigenin, casodex, omeprazol

[68–70]

17

Arginine dependency

increased

arginine deprivation diet,

pegylated arginine deiminase

[18–20]

[71–73]

18

Arginase/arginine/ornithine

increased

norvaline, N-omega-hydroxy-nor-arginine, boroargininre

[74–76]

19

Polyamine pathway:

Ornithine decarboxylase/putrescine

SAM decarboxylase

increased

DFMO (2-difluoromethylornithine),

MGBG methylglyoxal bis (guanylhydrazone),

4-amidinoindan-1one-2'-amidinhydrazone(alfa-fluoromethylhistidine)

[77–79]

20

Glutaminase/glutamate

increased

DON(6-diazo-5-oxo-l-norleucine),

riluzole, naftazone

[80].

21

Argininosuccinate synthetase

decreased

troglitazone

[81]