NPASS Compound

Natural Product: NPC157380

Natural Product ID	NPC157380
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cinobufagin
IUPAC Name	n.a.
Synonyms	Cinobufagin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL250785
PubChem CID	11969542
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001557] Bufanolides 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 66 71 0 0 0 0 0 0 0 0999 V2000 5.6630 -2.3479 -1.0231 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6706 -1.3673 -1.5815 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9999 -0.6402 -2.5441 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4122 -1.2399 -1.0724 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4105 -0.3822 -1.4883 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9136 0.3884 -0.2468 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0844 0.9702 0.3754 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3574 0.9388 1.7114 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5194 1.5321 2.1781 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4017 2.1546 1.3001 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4590 2.6969 1.7069 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0971 2.1580 0.0396 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0117 1.6123 -0.4577 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1756 -0.6892 0.4554 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1144 -1.7812 0.9369 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3594 -0.2814 1.6333 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0591 -0.8171 1.5433 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6355 -0.1667 0.3207 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9994 -0.8298 -0.8673 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2249 0.0553 -2.0715 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3653 0.9857 -1.7901 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5255 0.3126 -1.1125 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6468 1.3084 -0.9508 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4156 2.3183 0.1183 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7484 1.7795 1.3442 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8773 0.2926 1.3619 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1276 -0.3237 0.2021 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5314 -1.7825 0.1419 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6814 2.8307 0.4864 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3736 -1.3048 -0.6678 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2300 -1.2086 -1.9231 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9058 -2.3992 -1.3298 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8243 -3.1890 -1.7499 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2553 -2.8075 -0.0997 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6381 -1.8603 -0.8547 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6800 0.2854 -2.3175 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2199 1.1995 -0.6057 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7294 0.4901 2.4574 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7553 1.5170 3.2425 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8921 1.6941 -1.5273 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1255 -1.4375 1.1852 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7361 -2.2367 1.9037 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1279 -2.6670 0.2448 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7418 -0.7195 2.6075 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2492 0.8308 1.7216 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9603 -1.9203 1.4388 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5582 -0.5308 2.4853 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4139 0.9178 0.3854 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6368 -1.7468 -1.0634 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3478 0.6709 -2.3176 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4864 -0.5647 -2.9710 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0318 1.9127 -1.2834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7493 1.3290 -2.7935 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9074 -0.4569 -1.8450 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7894 1.7974 -1.9339 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5838 0.7227 -0.7570 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8373 3.1769 -0.2869 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6927 2.1192 1.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2535 2.1921 2.2579 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9588 0.0535 1.1862 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5587 -0.1983 2.2815 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7209 -2.4105 0.5340 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8058 -2.0875 -0.9016 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4570 -1.9808 0.7468 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3038 2.0654 0.6454 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7573 -0.9331 -2.8916 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 6 14 1 0 14 15 1 1 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 24 29 1 0 19 30 1 0 30 31 1 0 31 32 1 0 31 5 1 0 13 7 2 0 30 14 1 0 27 18 1 0 30 32 1 1 27 22 1 0 1 33 1 0 1 34 1 0 1 35 1 0 5 36 1 6 6 37 1 6 8 38 1 0 9 39 1 0 13 40 1 0 15 41 1 0 15 42 1 0 15 43 1 0 16 44 1 0 16 45 1 0 17 46 1 0 17 47 1 0 18 48 1 1 19 49 1 6 20 50 1 0 20 51 1 0 21 52 1 0 21 53 1 0 22 54 1 6 23 55 1 0 23 56 1 0 24 57 1 6 25 58 1 0 25 59 1 0 26 60 1 0 26 61 1 0 28 62 1 0 28 63 1 0 28 64 1 0 29 65 1 0 31 66 1 6 M END

Standard InCHIKey	SCULJPGYOQQXTK-OLRINKBESA-N
Standard InCHI	InChI=1S/C26H34O6/c1-14(27)31-22-21(15-4-7-20(29)30-13-15)25(3)11-9-18-19(26(25)23(22)32-26)6-5-16-12-17(28)8-10-24(16,18)2/h4,7,13,16-19,21-23,28H,5-6,8-12H2,1-3H3/t16-,17+,18+,19-,21+,22-,23-,24+,25-,26-/m1/s1
SMILES	CC(=O)O[C@@H]1[C@H](c2ccc(=O)oc2)[C@@]2(C)CC[C@H]3[C@@H](CC[C@@H]4C[C@H](CC[C@]34C)O)[C@]32[C@@H]1O3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.24	Volume:	449.109 ? Van der Waals volume.
Dense:	0.985	LogP:	2.882 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.099 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.549 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	30.0
TPSA:	89.27 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.554	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.202	Fsp³:	0.769
MCE-18:	175.348 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.861	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.369 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.05	Promiscuous compounds:	0.654

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.438	MDCK Permeability:	-5.06
Pgp-inhibitor:	0.437	Pgp-substrate:	0.005
PAMPA:	0.37 ? 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):	0.001
20% Bioavailability (F20%):	0.868	30% Bioavailability (F30%):	0.815
50% Bioavailability (F50%):	0.852

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.985
Plasma Protein Binding (PPB):	69.806%	Volume Distribution (VD):	-0.149
Fu:	31.629% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.001
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.01	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.037
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.632
HLM stability:	0.723 ? 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):

11.013

Half-life (T1/2):

1.433

ADMET: Toxicity

hERG Blockers:	0.028	hERG Blockers (10um):	0.115
Human Hepatotoxicity (H-HT):	0.472	Drug-induced Liver Injury (DILI):	0.396
AMES Toxicity:	0.552	Rat Oral Acute Toxicity:	0.442
Maximum Recommended Daily Dose:	0.892	Skin Sensitization:	0.847
Carcinogencity:	0.854	Eye Corrosion:	0.014
Eye Irritation:	0.634	Respiratory Toxicity:	0.48
Drug-induced Neurotoxicity:	0.103	Ototoxicity:	0.258
Hematotoxicity:	0.346	Drug-induced Nephrotoxicity:	0.79
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.155
A549 Cytotoxicity:	0.146	Hek293 Cytotoxicity:	0.5
BCF:	0.653 ? 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:	3.435 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.04 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.425 ? 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
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0040-4039(01)99818-1]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	roots	n.a.	n.a.	PMID[10346940]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11421725]
NPO33241	Bufo gargarizans	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575946]
NPO33241	Bufo gargarizans	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12141860]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15165135]
NPO3983	Piper futokadsura	Species	Piperaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[15635246]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15730237]
NPO664	Potentilla multifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17504571]
NPO20112	Syncephalastrum racemosum	Species	Syncephalastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18558746]
NPO9576	Bufo bufo	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21185919]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	twig	n.a.	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	twigs and leaves	Yunnan Province, China	2008-OCT	PMID[21954912]
NPO10672	Vitex megapotamica	Species	Lamiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[22708620]
NPO11981	Bufo gargarizans	Species	Bufonidae	Eukaryota	venom	n.a.	n.a.	PMID[24050254]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26722868]
NPO11981	Bufo gargarizans	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	PMID[28256122]
NPO18636	Cupressus macrocarpa	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32223924]
NPO2917	Artemisia oranensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20112	Syncephalastrum racemosum	Species	Syncephalastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO33241	Bufo gargarizans	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7543	Haplopappus venetus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10672	Vitex megapotamica	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26231	Vicia villosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12250	Strychnos fendleri	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11515	Streptomyces plumbeus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO664	Potentilla multifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6011	Pleurotus citrinopileatus	Species	Pleurotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3983	Piper futokadsura	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10043	Phebalium ozothamnoides	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6887	Lytanthus salicinus	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5177	Lecanora conizaeoides	Species	Lecanoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2498	Kochia trichophylla	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12735	Halimeda macroloba	Species	Halimedaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4797	Gavia immer	Species	Gaviidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18636	Cupressus macrocarpa	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9398	Cortinarius rubellus	Species	Cortinariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7884	Centaurea amara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12952	Cabucala madagascariensis	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9576	Bufo bufo	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21463	Aruncus dioicus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10672	Vitex megapotamica	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11981	Bufo gargarizans	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18636	Cupressus macrocarpa	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9576	Bufo bufo	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12250	Strychnos fendleri	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5177	Lecanora conizaeoides	Species	Lecanoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4797	Gavia immer	Species	Gaviidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20112	Syncephalastrum racemosum	Species	Syncephalastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10043	Phebalium ozothamnoides	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2498	Kochia trichophylla	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2917	Artemisia oranensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11515	Streptomyces plumbeus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO7884	Centaurea amara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6011	Pleurotus citrinopileatus	Species	Pleurotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11981	Bufo gargarizans	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12012	Saururus cernuus	Species	Saururaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6887	Lytanthus salicinus	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO12735	Halimeda macroloba	Species	Halimedaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9398	Cortinarius rubellus	Species	Cortinariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21463	Aruncus dioicus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18636	Cupressus macrocarpa	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO664	Potentilla multifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26231	Vicia villosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7543	Haplopappus venetus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3983	Piper futokadsura	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10672	Vitex megapotamica	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12952	Cabucala madagascariensis	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9576	Bufo bufo	Species	Bufonidae	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	9
Inhibition	2
Vmax/Km	8
IC50 ratio	4
IC50	26
Activity	1

Activity Type	# Activity
Individual protein	11
Cell line	23
Tissue	6
Others	8
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	Vmax/Km	=	1.4	uL/mg/min	PMID[21205911]
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	Vmax/Km	=	1.2	uL/mg/min	PMID[21205911]
NPT67	Individual protein	Cholinesterase	Equus caballus	Inhibition	=	3.97	%	PMID[23062825]
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Inhibition	=	10.6	%	PMID[23062825]
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	79.2	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	140.8	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	125.5	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	250.4	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	198.9	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	44.5	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	5200.0	nM	PMID[17911017]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	760.0	nM	PMID[17911017]
NPT547	Cell line	BGC-823	Homo sapiens	IC50	=	8500.0	nM	PMID[17911017]
NPT91	Cell line	KB	Homo sapiens	IC50	=	0.21	ug.mL-1	PMID[11575946]
NPT116	Cell line	HL-60	Homo sapiens	IC50	<	0.01	ug.mL-1	PMID[11575946]
NPT1366	Cell line	MH60	Mus musculus	IC50	>	25.0	ug.mL-1	PMID[11575946]
NPT1366	Cell line	MH60	Mus musculus	IC50	>	56300.0	nM	PMID[15620253]
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	=	100.0	nM	PMID[18558746]
NPT1317	Cell line	CCRF S-180	Mus musculus	IC50	>	50000.0	nM	PMID[23799775]
NPT1357	Cell line	H22	Mus musculus	IC50	>	50000.0	nM	PMID[23799775]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	1706.0	nM	PMID[23799775]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	2355.0	nM	PMID[23799775]
NPT81	Cell line	A549	Homo sapiens	IC50	=	6500.0	nM	PMID[24050254]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	5500.0	nM	PMID[24050254]
NPT81	Cell line	A549	Homo sapiens	IC50	=	2300.0	nM	PMID[32526552]
NPT2311	Cell line	Calu-3	Homo sapiens	IC50	=	2300.0	nM	PMID[32526552]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	2300.0	nM	PMID[32526552]
NPT1506	Cell line	SK-MES-1	Homo sapiens	IC50	=	2300.0	nM	PMID[32526552]
NPT2410	Cell line	NCI-H1299	Homo sapiens	IC50	=	2300.0	nM	PMID[32526552]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	390.0	nM	PMID[23799775]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	310.0	nM	PMID[23799775]
NPT626	Tissue	Liver microsome	Homo sapiens	Vmax/Km	=	57.4	uL/mg/min	PMID[21205911]
NPT626	Tissue	Liver microsome	Homo sapiens	Vmax/Km	=	47.2	uL/mg/min	PMID[21205911]
NPT23095	Cell line	BEAS-2B	Homo sapiens	IC50	=	22300.0	nM	PMID[32526552]
NPT24713	Tissue	Liver microsome	Canis lupus familiaris	Vmax/Km	=	129.4	uL/mg/min	PMID[21205911]
NPT24713	Tissue	Liver microsome	Canis lupus familiaris	Vmax/Km	=	387.9	uL/mg/min	PMID[21205911]
NPT897	Others	Monoclonal antibody (mAb)	n.a.	IC50 ratio	=	98000.0	n.a.	PMID[12109909]
NPT897	Others	Monoclonal antibody (mAb)	n.a.	IC50 ratio	=	1700.0	n.a.	PMID[12109909]
NPT897	Others	Monoclonal antibody (mAb)	n.a.	IC50 ratio	=	800.0	n.a.	PMID[12109909]
NPT897	Others	Monoclonal antibody (mAb)	n.a.	IC50 ratio	=	570.0	n.a.	PMID[12109909]
NPT2	Others	Unspecified	n.a.	IC50	=	0.00074	ug.mL-1	PMID[12459012]
NPT2	Others	Unspecified	n.a.	IC50	=	0.00092	ug.mL-1	PMID[12459012]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	199.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	89.1	nM	PubChem BioAssay data set
NPT625	Tissue	Liver	Mus musculus	Vmax/Km	=	644.6	uL/mg/min	PMID[21205911]
NPT625	Tissue	Liver	Mus musculus	Vmax/Km	=	595.0	uL/mg/min	PMID[21205911]
NPT22036	Cell line	HL	Homo sapiens	Activity	=	0.2	%	PMID[29043803]

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 NPC157380 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	10501
0.1-0.2	36850
0.2-0.3	2402
0.3-0.4	71
0.4-0.5	13
0.5-0.6	10
0.6-0.7	7
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8158	Intermediate Similarity	NPC35171
0.8133	Intermediate Similarity	NPC485877
0.8133	Intermediate Similarity	NPC16701
0.7037	Intermediate Similarity	NPC213761
0.6923	Remote Similarity	NPC185287
0.6923	Remote Similarity	NPC43063
0.6923	Remote Similarity	NPC79298
0.6333	Remote Similarity	NPC312481
0.6265	Remote Similarity	NPC75389
0.6098	Remote Similarity	NPC171126
0.6023	Remote Similarity	NPC485878
0.5938	Remote Similarity	NPC6193
0.5882	Remote Similarity	NPC159499
0.5765	Remote Similarity	NPC103491
0.5765	Remote Similarity	NPC278681
0.5747	Remote Similarity	NPC221414
0.5422	Remote Similarity	NPC189863
0.5222	Remote Similarity	NPC485880
0.5059	Remote Similarity	NPC275060
0.5059	Remote Similarity	NPC171014
0.5055	Remote Similarity	NPC485879

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC157380 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3368
0.1-0.2	5699
0.2-0.3	72
0.3-0.4	11
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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