Kratom (Mitragyna speciosa)
Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids CSV JSON

In vitro cytochrome P450 inhibition of major kratom alkaloids: mitragynine (MTG), speciogynine (SPG), speciocilliatine (SPC), corynantheidine (COR), 7-hydroxymitragynine (7HMG) and paynantheine (PAY) was evaluated using human liver microsomes (HLMs) to understand their drug-drug interaction potential. CYP450 isoform- specific substrates of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4/5 were incubated in HLMs with or without alkaloids. Preliminary CYP450 inhibition (IC50) data were generated for each of these isoforms. In addition, the type of inhibition and estimation of the inhibition constants (Ki) of MTG and COR were determined. Among the tested alkaloids, MTG and COR were potent inhibitors of CYP2D6 (IC50, 2.2 and 4.2 μM, respectively). Both MTG and COR exhibited competitive inhibition of CYP2D6 activity and the Ki were found to be 1.1 and 2.8 μM, respectively. SPG and PAY showed moderate inhibition of CYP2D6 activity. Additionally, moderate inhibitory effects by SPC, MTG, and SPG were observed on CYP2C19 activity. Interestingly, inhibition of only midazolam hydroxylase CYP3A4/5 activity by COR, PAY, and MTG was observed while no inhibitory effect was observed when testosterone was used as a probe substrate. In conclusion, MTG and COR may lead to clinically significant adverse drug interactions upon coadministration of drugs that are substantially metabolized by CYP2D6.

Kratom (Mitragyna speciosa)

31707106

2003905259

1 . Inhibition of Mitragynine for CYP2C8 (id=NPDI-J2PdQQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

amodiaquine

mitragynine

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

7 µM

1 - 100 µM

Control Experiment Information

2 . Inhibition of Speciociliatine for CYP2C8 (id=NPDI-JqmF7w)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

amodiaquine

speciociliatine

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

7 µM

0 - 100 µM

Control Experiment Information

3 . Inhibition of Corynantheidine for CYP2D6 (id=NPDI-qWS53g)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

dextromethorphan 1119510

corynantheidine

dextrorphan 4349487

  • CYP2D6 4173631

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

7 µM

1 - 100 µM

Control Experiment Information

4 . Inhibition of Mitragynine for CYP2D6 (id=NPDI-17YRkg)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

dextromethorphan 1119510

mitragynine

dextrorphan 4349487

  • CYP2D6 4173631

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

7 µM

1 - 100 µM

Control Experiment Information

5 . Inhibition of Paynantheine for CYP2D6 (id=NPDI-K9DvIg)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

dextromethorphan 1119510

paynantheine

dextrorphan 4349487

  • CYP2D6 4173631

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

7 µM

0 - 100 µM

Control Experiment Information

6 . Inhibition of Speciogynine for CYP2D6 (id=NPDI-Oq9KmA)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

dextromethorphan 1119510

speciogynine

dextrorphan 4349487

  • CYP2D6 4173631

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

7 µM

0 - 100 µM

Control Experiment Information

7 . Inhibition of Corynantheidine for CYP2C9 (id=NPDI-bXPXRQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

diclofenac 1124300

corynantheidine

4'-hydroxydiclofenac

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

6 µM

1 - 100 µM

Control Experiment Information

8 . Inhibition of Paynantheine for CYP2C9 (id=NPDI-4HfEdA)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

diclofenac 1124300

paynantheine

4'-hydroxydiclofenac

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

6 µM

0 - 100 µM

Control Experiment Information

9 . Inhibition of 7-hydroxymitragynine for CYP2C19 (id=NPDI-eMZPbA)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

mephenytoin, (s)-

7-hydroxymitragynine

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

60 min

NADPH

40 µM

1 - 100 µM

Control Experiment Information

10 . Inhibition of Mitragynine for CYP2C19 (id=NPDI-Ua1CeQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

mephenytoin, (s)-

mitragynine

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

60 min

NADPH

40 µM

Control Experiment Information

11 . Inhibition of Paynantheine for CYP2C19 (id=NPDI-wo-wRw)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

mephenytoin, (s)-

paynantheine

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

60 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

12 . Inhibition of Speciociliatine for CYP2C19 (id=NPDI-XQCOGw)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

mephenytoin, (s)-

speciociliatine

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

60 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

13 . Inhibition of Speicogynine for CYP2C19 (id=NPDI-WIpfxQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

mephenytoin, (s)-

speciogynine

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

60 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

14 . Inhibition of Corynantheidine for CYP3A4/5 (id=NPDI-7PU97Q)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

midazolam 708298

corynantheidine

1'-hydroxymidazolam

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

10 min

NADPH

4 µM

1 - 100 µM

Control Experiment Information

15 . Inhibition of Mitragynine for CYP3A4/5 (id=NPDI-c_gPeA)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

midazolam 708298

mitragynine

1'-hydroxymidazolam

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

10 min

NADPH

4 µM

1 - 100 µM

Control Experiment Information

16 . Inhibition of Paynantheine for CYP3A4/5 (id=NPDI-WakYGw)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

midazolam 708298

paynantheine

1'-hydroxymidazolam

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

10 min

NADPH

4 µM

0 - 100 µM

Control Experiment Information

17 . Inhibition of Speciociliatine for CYP3A4/5 (id=NPDI-TTv3Iw)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

midazolam 708298

speciociliatine

1'-hydroxymidazolam

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

10 min

NADPH

4 µM

0 - 100 µM

Control Experiment Information

18 . Inhibition of Speciogynine for CYP3A4/5 (id=NPDI-QQeDSQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

IC50 = 45 μM

midazolam 708298

speciogynine

1'-hydroxymidazolam

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

10 min

NADPH

4 µM

0 - 100 µM

Control Experiment Information

19 . Weak Inhibition of 7-hydroxymitragynine for CYP2C8 (id=NPDI-U-ajPw)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

amodiaquine

7-hydroxymitragynine

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

7 µM

1 - 100 µM

Control Experiment Information

20 . Weak Inhibition of Corynantheidine for CYP2C8 (id=NPDI-o56vpA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

amodiaquine

corynantheidine

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

7 µM

1 - 100 µM

Control Experiment Information

21 . Weak Inhibition of Paynantheine for CYP2C8 (id=NPDI-XeGihA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

amodiaquine

paynantheine

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

7 µM

0 - 100 µM

Control Experiment Information

22 . Weak Inhibition of Speciogynine for CYP2C8 (id=NPDI-B_7tOA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

amodiaquine

speciogynine

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

7 µM

0 - 100 µM

Control Experiment Information

23 . Weak Inhibition of 7-hydroxymitragynine for CYP2D6 (id=NPDI-cimaKA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

dextromethorphan 1119510

7-hydroxymitragynine

dextrorphan 4349487

  • CYP2D6 4173631

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

7 µM

1 - 100 µM

Control Experiment Information

24 . Weak Inhibition of Speciociliatine for CYP2D6 (id=NPDI-ULP_qQ)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

dextromethorphan 1119510

speciociliatine

dextrorphan 4349487

  • CYP2D6 4173631

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

7 µM

0 - 100 µM

Control Experiment Information

25 . Weak Inhibition of 7-hydroxymitragynine for CYP2C9 (id=NPDI-DLH-JQ)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

diclofenac 1124300

7-hydroxymitragynine

4'-hydroxydiclofenac

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

6 µM

1 - 100 µM

Control Experiment Information

26 . Weak Inhibition of Mitragynine for CYP2C9 (id=NPDI-0hNq0Q)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

diclofenac 1124300

mitragynine

4'-hydroxydiclofenac

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

6 µM

0 - 100 µM

Control Experiment Information

27 . Weak Inhibition of Speciociliatine for CYP2C9 (id=NPDI-Zvn2gg)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

diclofenac 1124300

speciociliatine

4'-hydroxydiclofenac

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S3

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

6 µM

0 - 100 µM

Control Experiment Information

28 . Weak Inhibition of Speciogynine for CYP2C9 (id=NPDI-sN1pZA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

diclofenac 1124300

speciogynine

4'-hydroxydiclofenac

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

6 µM

0 - 100 µM

Control Experiment Information

29 . Weak Inhibition of Corynantheidine for CYP2C19 (id=NPDI-aGXuxA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

mephenytoin, (s)-

corynantheidine

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

60 min

NADPH

40 µM

1 - 100 µM

Control Experiment Information

30 . Weak Inhibition of 7-hydroxymitragynine for CYP3A4/5 (id=NPDI-olaGPQ)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

midazolam 708298

7-hydroxymitragynine

1'-hydroxymidazolam

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

10 min

NADPH

4 µM

1 - 100 µM

Control Experiment Information

31 . Weak Inhibition of 7-hydroxymitragynine for CYP1A2 (id=NPDI-1vxnrQ)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

phenacetin 19033710

7-hydroxymitragynine

acetaminophen 1125315

  • CYP1A2 4312402

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

40 µM

1 - 100 µM

Control Experiment Information

32 . Weak Inhibition of Cornantheidine for CYP1A2 (id=NPDI-1Cjyxg)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

phenacetin 19033710

corynantheidine

acetaminophen 1125315

  • CYP1A2 4312402

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

40 µM

1 - 100 µM

Control Experiment Information

33 . Weak Inhibition of Mitragynine for CYP1A2 (id=NPDI-laH1lA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

phenacetin 19033710

mitragynine

acetaminophen 1125315

  • CYP1A2 4312402

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

34 . Weak Inhibition of Paynantheine for CYP1A2 (id=NPDI-V_oQog)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

phenacetin 19033710

paynantheine

acetaminophen 1125315

  • CYP1A2 4312402

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

35 . Weak Inhibition of Speciociliatine for CYP1A2 (id=NPDI-zKam8g)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

phenacetin 19033710

speciociliatine

acetaminophen 1125315

  • CYP1A2 4312402

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S3 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

36 . Weak Inhibition of Speciogynine for CYP1A2 (id=NPDI-_MFsyA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

phenacetin 19033710

speciogynine

acetaminophen 1125315

  • CYP1A2 4312402

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 30 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

15 min

NADPH

40 µM

0 - 100 µM

Control Experiment Information

37 . Weak Inhibition of 7-hydroxymitragynine for CYP3A4/5 (id=NPDI-iASYyA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

testosterone

7-hydroxymitragynine

6beta-hydroxytestosterone

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S4 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

100 µM

1 - 100 µM

Control Experiment Information

38 . Weak Inhibition of Corynantheidine for CYP3A4/5 (id=NPDI-qMnZyA)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

testosterone

corynantheidine

6beta-hydroxytestosterone

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

100 µM

1 - 100 µM

Control Experiment Information

39 . Weak Inhibition of Mitragynine for CYP3A4/5 (id=NPDI-BLzT_g)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

testosterone

mitragynine

6beta-hydroxytestosterone

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure 2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

100 µM

1 - 100 µM

Control Experiment Information

40 . Weak Inhibition of Paynantheine for CYP3A4/5 (id=NPDI-aNb3lw)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

testosterone

paynantheine

6beta-hydroxytestosterone

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S5 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

100 µM

0 - 100 µM

Control Experiment Information

41 . Weak Inhibition of Speciociliatine for CYP3A4/5 (id=NPDI-2seH4Q)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

testosterone

speciociliatine

6beta-hydroxytestosterone

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S3 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

100 µM

0 - 100 µM

Control Experiment Information

42 . Weak Inhibition of Speciogynine for CYP3A4/5 (id=NPDI-P2Nw6g)

In Vitro Enzyme Inhibition Experiment

Negligible Inhibition was detected.  Cutoff used —

IC50 = 45 μM

testosterone

speciogynine

6beta-hydroxytestosterone

  • CYP3A4 4306811
  • CYP3A5

Cell fraction Pooled human liver microsomes -7999662

Results

% result estimated from Figure S2 at around 100 µM

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/ml

200 µL

5 min

NADPH

100 µM

0 - 100 µM

Control Experiment Information