Table 1 Noteworthy combination results from >4,000 discreet combinations testeda

From: High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations

Drug Ab

Mechanistic Classc

Drug Bb

Mechanistic Classc

Comb. Effect (DBSumNeg)d

In vivo validation?e

ATM

Endoperoxide

Alvespimycin

HSP90 inhib.

−6.08

N.T.

ATM

Endoperoxide

M.B.

oxid. stress inducer

−5.97

N.T.

ATM

Endoperoxide

NVP-AUY992

HSP90 inhib.

−6.84

N.T.

ATM

Endoperoxide

NVP-BGT226

PI3K inhib.

−8.29

Yes

ATM

Endoperoxide

Reserpine

Ca2+ channel inhib.

−9.71

N.T.

ATM

Endoperoxide

Quisinostat

HDAC inhib.

−5.77

N.T.

ATM

Endoperoxide

KN-62

CaM kinase II inhib.

−10.92

N.T.

ATM

Endoperoxide

LUM

Heme conversion inhib.

−4.05

Yes

AS

Endoperoxide

MFQ

Heme conversion inhib.

−5.72

N.T.

AS

Endoperoxide

Propafenone

Na+ channel inhib.

−9.51

N.T.

DHA

Endoperoxide

LUM

Heme conversion inhib.

−4.94

N.T.

DHA

Endoperoxide

M.B.

oxid. stress inducer

−3.49

N.T.

LUM

Heme conversion inhib.

NVP-BGT226

PI3K inhib.

−2.33

Yes

LUM

Heme conversion inhib.

Manidipine

Ca2+ channel inhib.

−7.69

N.T.

LUM

Heme conversion inhib.

Rifampin

Protein synthesis inhib.

−4.99

N.T.

LUM

Heme conversion inhib.

Midostaurin

multikinase inhib.

−4.7

N.T.

MFQ

Heme conversion inhib.

Nicardipine

Ca2+ channel inhib.

−7.45

N.T.

MFQ

Heme conversion inhib.

Midostaurin

multikinase inhib.

−4.76

N.T.

AQ

Heme conversion inhib.

BIX-01294

methylation inhib.

−4.38

N.T.

Atovaquone

e− transport chain inhib.

ML238

e− transport chain inhib.

−7.78

N.T.

Atovaquone

e− transport chain inhib.

Decoquinate

e− transport chain inhib.

−3.28

N.T.

Atovaquone

e− transport chain inhib.

Genz-669178

PfDHODH inhib.

−3.18

N.T.

ML238

e− transport chain inhib.

Genz-669178

PfDHODH inhib.

−5.4

N.T.

NITD-609

Protein synthesis/PfATPase4 inhib.

Trichostatin A

HDAC inhib.

−2.43

N.T.

Leptomycin B

Nuclear export inhib.

Nanchangmycin

Antibiotic

−3.57

N.T.

  1. aData is against P. falciparum 3D7 and represents the lowest values from duplicate screens. Complete data sets can be found at https://tripod.nih.gov/matrix-client/rest/matrix/blocks/1761/table.
  2. bArtemether (ATM), artesunate (AS), dihydroartemisinin (DHA), lumefantrine (LUM), mefloquine (MFQ), amodiaquine (AQ), methylene blue (M.B.).
  3. cMechanistic class reflects general terms and is not intended to cover all putatively contributing pharmacology’s of the drugs listed (may reflect hypothesized mechanism based on mammalian target).
  4. dCombination effect reflects the DBSumNeg value.
  5. eYes indicates in vivo study presented in this study only. N.T. (not tested).
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