NPASS Compound

Natural Product: NPC238665

Natural Product ID	NPC238665
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZPINJJOPURFFNV-DQEHQXCCSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	21827796
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003423] 7,7'-epoxylignans

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 63 65 0 0 0 0 0 0 0 0999 V2000 -0.6222 -3.0814 0.8453 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0326 -1.9861 0.0495 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9785 -2.4676 -0.9938 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3236 -3.4179 -1.9777 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1390 -1.1638 -1.7428 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1839 -0.2726 -1.2356 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2573 -0.7153 -0.5364 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2397 0.1569 -0.0491 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1165 1.4933 -0.2831 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0270 2.0064 -1.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0714 1.0713 -1.4643 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9367 3.2847 -1.2064 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8356 4.5508 -1.4173 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0863 2.3853 0.1932 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9271 2.9325 1.4687 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3148 -0.3623 0.6593 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4077 -1.7386 0.8787 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0959 -0.5129 -1.6382 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9535 -1.2897 -0.8946 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0616 -0.5568 -0.2969 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9245 0.6610 0.3321 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0232 1.3066 0.8681 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2952 0.7379 0.7838 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4368 -0.4803 0.1562 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3345 -1.1082 -0.3711 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6728 -1.1092 0.0346 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8281 -2.3436 -0.5993 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4004 1.3640 1.3097 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8332 1.1556 2.6361 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9348 2.5297 1.5074 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7344 3.2185 1.6736 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2911 -2.6150 1.6096 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2239 -3.8192 0.3164 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2027 -3.5467 1.4441 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5154 -1.3112 0.7143 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8706 -2.8836 -0.5535 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5155 -3.9822 -1.5847 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0007 -2.9325 -2.9188 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1007 -4.1744 -2.2859 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2680 -1.3450 -2.8397 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4159 -1.7376 -0.3261 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2570 1.5221 -2.0080 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7725 4.9411 -1.6246 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1122 5.1687 -0.4924 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4785 5.0278 -2.2214 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5406 2.3565 2.2007 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2259 3.9853 1.4866 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8503 2.8891 1.7723 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3795 -2.2480 -0.1248 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3359 -2.0466 1.3785 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5365 -2.1573 1.4504 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3161 -2.0932 -1.6087 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9332 1.1095 0.4011 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4596 -2.0643 -0.8605 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1644 -3.0868 -0.1043 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8835 -2.6759 -0.5402 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5818 -2.2485 -1.6906 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9955 1.0580 3.3561 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4465 2.0149 3.0087 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4942 0.2632 2.6114 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9051 4.3349 1.7295 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0426 3.0920 0.8264 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2700 2.9569 2.6619 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 3 5 1 0 5 6 1 0 6 7 2 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 9 14 1 0 14 15 1 0 8 16 1 0 16 17 1 0 5 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 23 28 1 0 28 29 1 0 22 30 1 0 30 31 1 0 19 2 1 0 25 20 1 0 11 6 1 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 1 3 36 1 1 4 37 1 0 4 38 1 0 4 39 1 0 5 40 1 6 7 41 1 0 11 42 1 0 13 43 1 0 13 44 1 0 13 45 1 0 15 46 1 0 15 47 1 0 15 48 1 0 17 49 1 0 17 50 1 0 17 51 1 0 19 52 1 6 21 53 1 0 25 54 1 0 27 55 1 0 27 56 1 0 27 57 1 0 29 58 1 0 29 59 1 0 29 60 1 0 31 61 1 0 31 62 1 0 31 63 1 0 M END

Standard InCHIKey	ZPINJJOPURFFNV-DQEHQXCCSA-N
Standard InCHI	InChI=1S/C24H32O7/c1-13-14(2)22(16-11-19(27-5)24(30-8)20(12-16)28-6)31-21(13)15-9-17(25-3)23(29-7)18(10-15)26-4/h9-14,21-22H,1-8H3/t13-,14+,21-,22+
SMILES	C[C@H]1[C@@H](C)[C@H](c2cc(c(c(c2)OC)OC)OC)O[C@@H]1c1cc(c(c(c1)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.21	Volume:	443.704 ? Van der Waals volume.
Dense:	0.974	LogP:	2.279 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.645 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.229 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	17.0
TPSA:	64.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.592	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.311	Fsp³:	0.5
MCE-18:	67.667 ? 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:	0.15	Fluc inhibitor:	0.442 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.043 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.065 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.332	Promiscuous compounds:	0.149

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.947	MDCK Permeability:	-4.711
Pgp-inhibitor:	0.236	Pgp-substrate:	0.017
PAMPA:	0.003 ? 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%):	0.006	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.526

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.916	MRP1:	1.0
Plasma Protein Binding (PPB):	92.846%	Volume Distribution (VD):	0.084
Fu:	5.084% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.95
OATP1B3 inhibitor:	0.975	BCRP inhibitor:	0.102
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.994	CYP1A2-substrate:	0.017
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.993
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.48
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.018 ? 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):

7.002

Half-life (T1/2):

1.514

ADMET: Toxicity

hERG Blockers:	0.283	hERG Blockers (10um):	0.646
Human Hepatotoxicity (H-HT):	0.56	Drug-induced Liver Injury (DILI):	0.724
AMES Toxicity:	0.373	Rat Oral Acute Toxicity:	0.379
Maximum Recommended Daily Dose:	0.49	Skin Sensitization:	0.348
Carcinogencity:	0.667	Eye Corrosion:	0.044
Eye Irritation:	0.546	Respiratory Toxicity:	0.732
Drug-induced Neurotoxicity:	0.799	Ototoxicity:	0.474
Hematotoxicity:	0.714	Drug-induced Nephrotoxicity:	0.368
Genotoxicity:	0.071	RPMI-8226 Immunitoxicity:	0.232
A549 Cytotoxicity:	0.283	Hek293 Cytotoxicity:	0.548
BCF:	2.482 ? 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:	3.968 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.369 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.617 ? 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
NPO4331	Plakortis lita	Species	Plakinidae	Eukaryota	n.a.	Palauan	n.a.	PMID[10479343]
NPO4331	Plakortis lita	Species	Plakinidae	Eukaryota	n.a.	Okinawan	n.a.	PMID[11277756]
NPO25126	Sarcophyton latum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16724849]
NPO25126	Sarcophyton latum	Species	Orchidaceae	Eukaryota	n.a.	Hainan soft coral	n.a.	PMID[16724849]
NPO9339	Beilschmiedia tsangii	Species	Lauraceae	Eukaryota	roots	Mudan, Pingtung County, Taiwan	2009-APR	PMID[21846089]
NPO9339	Beilschmiedia tsangii	Species	Lauraceae	Eukaryota	n.a.	root	n.a.	PMID[21846089]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27214307]
NPO2861	Pentaceraster regulus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[28981263]
NPO4331	Plakortis lita	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9722494]
NPO7401	Centaurea dealbata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25126	Sarcophyton latum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1462	Amomum sulcatum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO772	Bosistoa floydii	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO134	Cassia artemisioides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6053	Veronica intercedens	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6305	Euphorbia jaxartica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3331	Hedysarum sachalinense	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5582	Inocybe aeruginascens	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6791	Malva rotundifolia	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO569	Micromelum integerrimum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9215	Papaver glaucum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2861	Pentaceraster regulus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4331	Plakortis lita	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO345	Quercus laurifolia	Species	Fagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4888	Salvia divaricata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5844	Schlumbergera truncata	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27884	Sphacelaria arctica	Species	Sphacelariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO569	Micromelum integerrimum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5844	Schlumbergera truncata	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO569	Micromelum integerrimum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO569	Micromelum integerrimum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO6305	Euphorbia jaxartica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3331	Hedysarum sachalinense	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5582	Inocybe aeruginascens	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1462	Amomum sulcatum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9215	Papaver glaucum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27884	Sphacelaria arctica	Species	Sphacelariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4888	Salvia divaricata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2861	Pentaceraster regulus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4331	Plakortis lita	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO345	Quercus laurifolia	Species	Fagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5844	Schlumbergera truncata	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6791	Malva rotundifolia	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO134	Cassia artemisioides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7401	Centaurea dealbata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO569	Micromelum integerrimum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25126	Sarcophyton latum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9339	Beilschmiedia tsangii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6053	Veronica intercedens	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO772	Bosistoa floydii	Species	Rutaceae	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

Molecular-level activity

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

In vitro activity

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

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 NPC238665 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	27583
0.1-0.2	19921
0.2-0.3	2028
0.3-0.4	220
0.4-0.5	49
0.5-0.6	28
0.6-0.7	12
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC9891
1.0	High Similarity	NPC88297
1.0	High Similarity	NPC186845
0.7941	Intermediate Similarity	NPC50683
0.7941	Intermediate Similarity	NPC72046
0.7941	Intermediate Similarity	NPC261812
0.7941	Intermediate Similarity	NPC112571
0.7941	Intermediate Similarity	NPC65183
0.7941	Intermediate Similarity	NPC285725
0.7714	Intermediate Similarity	NPC204215
0.7647	Intermediate Similarity	NPC31530
0.7105	Intermediate Similarity	NPC175067
0.6765	Remote Similarity	NPC216929
0.6765	Remote Similarity	NPC312713
0.6765	Remote Similarity	NPC126935
0.6765	Remote Similarity	NPC65933
0.6765	Remote Similarity	NPC57268
0.6765	Remote Similarity	NPC172676
0.6341	Remote Similarity	NPC136750
0.6341	Remote Similarity	NPC266848
0.6111	Remote Similarity	NPC475856
0.6	Remote Similarity	NPC281864
0.6	Remote Similarity	NPC328682
0.6	Remote Similarity	NPC54321
0.5778	Remote Similarity	NPC177868
0.5714	Remote Similarity	NPC158331
0.561	Remote Similarity	NPC57119
0.561	Remote Similarity	NPC158471
0.561	Remote Similarity	NPC326095
0.561	Remote Similarity	NPC226862
0.5385	Remote Similarity	NPC271208
0.5385	Remote Similarity	NPC233224
0.5385	Remote Similarity	NPC610263
0.5366	Remote Similarity	NPC213482
0.525	Remote Similarity	NPC282703
0.525	Remote Similarity	NPC184733
0.525	Remote Similarity	NPC473092
0.525	Remote Similarity	NPC473093
0.525	Remote Similarity	NPC8050
0.525	Remote Similarity	NPC128208
0.525	Remote Similarity	NPC129570
0.525	Remote Similarity	NPC63238
0.525	Remote Similarity	NPC602603
0.5227	Remote Similarity	NPC487684
0.5116	Remote Similarity	NPC1474
0.5116	Remote Similarity	NPC216434
0.5116	Remote Similarity	NPC103448
0.5116	Remote Similarity	NPC606558
0.5111	Remote Similarity	NPC11258
0.5111	Remote Similarity	NPC21867
0.5111	Remote Similarity	NPC45774
0.5111	Remote Similarity	NPC74914

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC238665 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5108
0.1-0.2	3897
0.2-0.3	134
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