NPASS Compound

Natural Product: NPC138487

Natural Product ID	NPC138487
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VZTUIEROBZXUFA-MRXNPFEDSA-N
IUPAC Name	n.a.
Synonyms	(+)-Tetrahydroberberine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL476501
PubChem CID	443422
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001909] Protoberberine alkaloids and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 46 50 0 0 0 0 0 0 0 0999 V2000 6.4020 0.4986 -1.0666 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3780 -0.0183 -0.2785 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0242 0.2069 -0.5064 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5496 0.9743 -1.5486 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1877 1.1505 -1.7075 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2571 0.5852 -0.8576 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2157 0.7990 -1.0616 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9289 -0.2751 -0.3123 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3917 -0.0884 -0.2527 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2523 -0.7503 -1.0932 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6395 -0.5490 -1.0065 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1536 0.3192 -0.0723 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2926 0.9801 0.7671 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9073 0.7794 0.6808 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0276 1.5272 1.6193 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6109 1.0656 1.6348 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4920 -0.2403 1.0824 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7927 -0.8430 1.1684 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7261 -0.1826 0.1856 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0958 -0.3580 0.3428 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5138 -1.1538 1.4284 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6809 -2.5579 1.2670 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5564 0.3167 -0.2189 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9327 -0.8080 -0.9671 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7291 -1.0597 -1.6987 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6614 -0.1977 -1.8870 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1417 1.5051 -1.3885 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3181 0.5772 -0.4112 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2747 1.4278 -2.2290 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8322 1.7588 -2.5350 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5301 1.8204 -0.8370 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3574 0.6793 -2.1763 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6410 -1.2470 -0.7659 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8617 -1.4385 -1.8355 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7056 1.6588 1.4962 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1174 2.6375 1.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4312 1.3819 2.6643 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0056 1.8346 1.1277 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1900 1.0141 2.6794 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2347 -0.8243 2.1743 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7003 -1.8944 0.8081 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7278 -3.1101 1.3665 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0922 -2.7615 0.2548 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3818 -2.8900 2.0636 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7820 -0.5820 -1.6497 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2317 -1.6686 -0.3492 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 12 23 1 0 23 24 1 0 24 25 1 0 20 3 1 0 19 6 1 0 17 8 1 0 14 9 1 0 25 11 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 5 30 1 0 7 31 1 0 7 32 1 0 8 33 1 6 10 34 1 0 13 35 1 0 15 36 1 0 15 37 1 0 16 38 1 0 16 39 1 0 18 40 1 0 18 41 1 0 22 42 1 0 22 43 1 0 22 44 1 0 24 45 1 0 24 46 1 0 M END

Standard InCHIKey	VZTUIEROBZXUFA-MRXNPFEDSA-N
Standard InCHI	InChI=1S/C20H21NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,8-9,16H,5-7,10-11H2,1-2H3/t16-/m1/s1
SMILES	COc1ccc2C[C@@H]3c4cc5c(cc4CCN3Cc2c1OC)OCO5

Calculated Properties

Physi-Chem Properties

Molecular Weight:	339.15	Volume:	342.033 ? Van der Waals volume.
Dense:	0.992	LogP:	2.301 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.455 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.163 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	25.0
TPSA:	40.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.841	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.982	Fsp³:	0.4
MCE-18:	85.714 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.231	Fluc inhibitor:	0.243 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.406 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.387 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.175

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.749	MDCK Permeability:	-4.75
Pgp-inhibitor:	0.412	Pgp-substrate:	0.131
PAMPA:	0.007 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.009	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.514

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.996	MRP1:	0.964
Plasma Protein Binding (PPB):	89.858%	Volume Distribution (VD):	0.22
Fu:	10.257% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.354
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.914
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.087
CYP2C9-inhibitor:	0.995	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.435	CYP3A4-substrate:	0.97
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.509 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

6.103

Half-life (T1/2):

1.454

ADMET: Toxicity

hERG Blockers:	0.418	hERG Blockers (10um):	0.619
Human Hepatotoxicity (H-HT):	0.592	Drug-induced Liver Injury (DILI):	0.183
AMES Toxicity:	0.688	Rat Oral Acute Toxicity:	0.48
Maximum Recommended Daily Dose:	0.741	Skin Sensitization:	0.689
Carcinogencity:	0.88	Eye Corrosion:	0.006
Eye Irritation:	0.583	Respiratory Toxicity:	0.735
Drug-induced Neurotoxicity:	0.77	Ototoxicity:	0.447
Hematotoxicity:	0.282	Drug-induced Nephrotoxicity:	0.352
Genotoxicity:	0.385	RPMI-8226 Immunitoxicity:	0.075
A549 Cytotoxicity:	0.121	Hek293 Cytotoxicity:	0.398
BCF:	2.249 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.371 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.133 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.371 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0168-9452(00)00306-X]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/np990201k]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	DOI[10.5012/bkcs.2003.24.11.1699]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	Needles	n.a.	n.a.	PMID[11325226]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11830162]
NPO29080	Ulex airensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11858751]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[12510838]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12809361]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	Roots; Rhizomes	n.a.	n.a.	PMID[15568768]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[15646793]
NPO25373	Stereocaulon alpinum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18288807]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	tubers	n.a.	n.a.	PMID[20594848]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21625478]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[21657081]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21661731]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22737858]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23194502]
NPO26428	Ligularia sagitta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24913558]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	rhizome	n.a.	PMID[25277281]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	root	n.a.	n.a.	PMID[25597012]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	tuber	n.a.	PMID[25670016]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27444348]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29091439]
NPO25373	Stereocaulon alpinum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29878768]
NPO22441	Senna spectabilis	Species	Fabaceae	Eukaryota	flowers	n.a.	n.a.	PMID[30413343]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[31464439]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32058719]
NPO21029	Euphorbia prostrata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36447306]
NPO16414	Thuja plicata	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36985451]
NPO16414	Thuja plicata	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38794396]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	roots	n.a.	n.a.	PMID[9784149]
NPO25657	Mezzettia leptopoda	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9868159]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16414	Thuja plicata	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24476	Phellodendron amurense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22242	Phellodendron chinense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26538	Phellodendron chinese	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22441	Senna spectabilis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23223	Symphytum officinale	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21029	Euphorbia prostrata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29080	Ulex airensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11457	Chelidonium majus	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25881	Stachys plumosa	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24480	Diospyros ebenum	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8144	Labidiaster annulatus	Species	Labidiasteridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25373	Stereocaulon alpinum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24480	Diospyros ebenum	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11457	Chelidonium majus	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15694	Corydalis cheilanthifolia	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24476	Phellodendron amurense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22242	Phellodendron chinense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23223	Symphytum officinale	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8994	Berberis kawakamii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1106	Artabotrys maingayi	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19660	Corydalis rotundatour	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16414	Thuja plicata	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14096	Zanthoxylum veneficium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26428	Ligularia sagitta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23223	Symphytum officinale	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22242	Phellodendron chinense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24087	Psacalium peltatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11457	Chelidonium majus	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14096	Zanthoxylum veneficium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15694	Corydalis cheilanthifolia	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24476	Phellodendron amurense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25373	Stereocaulon alpinum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16414	Thuja plicata	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25166	Corydalis ophiocarpa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8994	Berberis kawakamii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24480	Diospyros ebenum	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19660	Corydalis rotundatour	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26428	Ligularia sagitta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1106	Artabotrys maingayi	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26230	Lappula echinata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22242	Phellodendron chinense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24476	Phellodendron amurense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11457	Chelidonium majus	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24480	Diospyros ebenum	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23223	Symphytum officinale	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25166	Corydalis ophiocarpa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22242	Phellodendron chinense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2341	Fibraurea recisa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11457	Chelidonium majus	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24476	Phellodendron amurense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26538	Phellodendron chinese	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24480	Diospyros ebenum	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24087	Psacalium peltatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16414	Thuja plicata	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7177	Inocybe rimosa	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24868	Streptomyces aizunensis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO13962	Corydalis turtschaninovii	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25484	Bumelia obtusifolia	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO25373	Stereocaulon alpinum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1106	Artabotrys maingayi	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25624	Teclea sudanica	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25657	Mezzettia leptopoda	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO336	Chaetomorpha moniligera	Species	Cladophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25166	Corydalis ophiocarpa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22242	Phellodendron chinense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24758	Angelica dahurica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25881	Stachys plumosa	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25345	Corydalis ternata	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25316	Lasius niger	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26230	Lappula echinata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21029	Euphorbia prostrata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29080	Ulex airensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11778	Ramaria flava	Species	Gomphaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26428	Ligularia sagitta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22441	Senna spectabilis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8144	Labidiaster annulatus	Species	Labidiasteridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18332	Amaryllis radiata	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23223	Symphytum officinale	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29053	Dictyostelium longosporum	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13290	Taxus canadensis	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8994	Berberis kawakamii	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24476	Phellodendron amurense	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14648	Aspilia hispidantha	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15694	Corydalis cheilanthifolia	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO827	Corydalis yanhusuo	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Potency	20
AC50	4
Ki	1
Inhibition	4

Activity Type	# Activity
Individual protein	20
Organism	4
Others	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT213	Individual protein	Cytochrome P450 2C19	Homo sapiens	Potency	=	1258.9	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	Potency	=	7943.3	nM	PubChem BioAssay data set
NPT110	Individual protein	Cytochrome P450 2D6	Homo sapiens	Potency	=	63.1	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	AC50	=	7943.28	nM	PubChem BioAssay data set
NPT213	Individual protein	Cytochrome P450 2C19	Homo sapiens	AC50	=	1258.93	nM	PubChem BioAssay data set
NPT208	Individual protein	Cytochrome P450 1A2	Homo sapiens	AC50	=	1584.89	nM	PubChem BioAssay data set
NPT110	Individual protein	Cytochrome P450 2D6	Homo sapiens	AC50	=	63.1	nM	PubChem BioAssay data set
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	4466.8	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	1835.6	nM	PubChem BioAssay data set
NPT159	Individual protein	Aberrant vpr protein	Human immunodeficiency virus 1	Potency	n.a.	25118.9	nM	PubChem BioAssay data set
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	Ki	>	5000.0	nM	PMID[23332346]
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	Inhibition	=	75.5	%	PMID[23332346]
NPT243	Individual protein	Dopamine D2 receptor	Homo sapiens	Inhibition	=	26.6	%	PMID[23332346]
NPT290	Individual protein	Serotonin 2a (5-HT2a) receptor	Homo sapiens	Inhibition	=	18.3	%	PMID[23332346]
NPT483	Individual protein	Prelamin-A/C	Homo sapiens	Potency	=	354.8	nM	PubChem BioAssay data set
NPT444	Individual protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	1412.5	nM	PubChem BioAssay data set
NPT478	Individual protein	Ataxin-2	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT92	Individual protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	Inhibition	=	34.5	%	PMID[23332346]
NPT532	Individual protein	Lysine-specific demethylase 4A	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	369.6	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	720.8	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	2869.5	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	3696.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	=	580.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	11220.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	10000.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	39810.7	nM	PubChem BioAssay data set

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC138487 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	34249
0.1-0.2	14094
0.2-0.3	1246
0.3-0.4	175
0.4-0.5	58
0.5-0.6	13
0.6-0.7	12
0.7-0.8	0
0.8-0.85	1
0.85-0.9	6
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC216459
1.0	High Similarity	NPC41178
0.8727	High Similarity	NPC326205
0.8704	High Similarity	NPC31311
0.8704	High Similarity	NPC234392
0.8654	High Similarity	NPC210437
0.8654	High Similarity	NPC16107
0.8654	High Similarity	NPC106295
0.8491	Intermediate Similarity	NPC51957
0.7213	Intermediate Similarity	NPC606650
0.7031	Intermediate Similarity	NPC232514
0.6885	Remote Similarity	NPC204828
0.6885	Remote Similarity	NPC295691
0.6885	Remote Similarity	NPC207757
0.6885	Remote Similarity	NPC54379
0.6885	Remote Similarity	NPC5238
0.6825	Remote Similarity	NPC276944
0.6825	Remote Similarity	NPC238530
0.6667	Remote Similarity	NPC2314
0.6508	Remote Similarity	NPC264850
0.6452	Remote Similarity	NPC27887
0.6129	Remote Similarity	NPC39701
0.6129	Remote Similarity	NPC184026
0.5965	Remote Similarity	NPC128019
0.5821	Remote Similarity	NPC146288
0.5781	Remote Similarity	NPC276588
0.5781	Remote Similarity	NPC127674
0.5781	Remote Similarity	NPC278799
0.5625	Remote Similarity	NPC7467
0.5606	Remote Similarity	NPC67978
0.5303	Remote Similarity	NPC469817
0.5075	Remote Similarity	NPC189266
0.5075	Remote Similarity	NPC172765
0.5075	Remote Similarity	NPC2413
0.5075	Remote Similarity	NPC110416
0.5072	Remote Similarity	NPC93593

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC138487 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5002
0.1-0.2	3949
0.2-0.3	177
0.3-0.4	19
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8654	High Similarity	NPD4584	Phase 2

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data