NPASS Compound

Natural Product: NPC287884

Natural Product ID	NPC287884
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KVPJDVHJFGPPAB-AXRGIPJOSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3121245
PubChem CID	76317993
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 62 68 0 0 0 0 0 0 0 0999 V2000 6.5359 3.5825 -0.0578 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6860 2.5037 0.1871 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9637 2.0140 -0.8574 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1022 0.9370 -0.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9612 0.3497 0.5803 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6971 0.8543 1.6276 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5566 1.9260 1.4365 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0512 -0.7892 0.7948 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7007 -2.0992 0.3785 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6924 -3.1885 0.6803 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3991 -2.9019 -0.0261 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9736 -1.6015 -0.2656 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8001 -0.5894 0.1788 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2006 -1.3083 -0.9072 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0017 -2.3526 -1.3379 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5952 -3.6656 -1.1089 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5921 -3.9242 -0.4602 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0358 -5.2219 -0.2109 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1479 -1.8005 -1.9660 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3281 -0.5778 -1.2751 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8878 -0.1172 -1.2928 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6025 0.1135 -2.6649 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7026 1.1394 -0.6158 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2430 1.5033 0.0905 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8121 2.1109 -0.8093 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7347 3.3994 -0.3274 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5891 3.8260 0.3663 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7462 4.3208 -0.4917 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8782 3.9234 -1.1688 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9456 2.6319 -1.6469 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9402 1.7014 -1.4887 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0540 0.3892 -1.9961 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9388 4.8263 -1.3629 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8726 -0.8924 0.0263 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2400 -0.8201 1.2342 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8561 -1.1453 2.4203 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1607 -1.5628 2.4181 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8302 -1.6480 1.2211 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2003 -1.3211 0.0598 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8066 -1.8999 3.6254 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1647 4.3740 -0.5841 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0424 2.4436 -1.8470 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5561 0.5885 -1.5111 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6291 0.4407 2.6070 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1526 2.3523 2.2333 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8324 -0.9098 1.8955 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5554 -2.2572 1.0825 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0132 -2.0934 -0.6687 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5243 -3.2113 1.7784 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0686 -4.1876 0.3859 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2185 -4.5095 -1.4439 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0578 -5.9009 -0.9707 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4052 0.4354 -3.1275 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0274 4.5141 -0.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6839 5.3343 -0.1120 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8661 2.3680 -2.1771 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2245 5.4526 -0.6195 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2301 -0.4986 1.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3278 -1.0784 3.3678 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8718 -1.9799 1.2056 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7843 -1.4088 -0.8608 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9310 -2.8933 3.8552 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 15 19 1 0 19 20 1 0 20 21 1 0 21 22 1 6 21 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 29 33 1 0 20 34 1 1 34 35 2 0 35 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 37 40 1 0 7 2 1 0 13 8 1 0 21 14 1 0 31 25 1 0 39 34 1 0 17 11 1 0 32 20 1 0 1 41 1 0 3 42 1 0 4 43 1 0 6 44 1 0 7 45 1 0 8 46 1 1 9 47 1 0 9 48 1 0 10 49 1 0 10 50 1 0 16 51 1 0 18 52 1 0 22 53 1 0 27 54 1 0 28 55 1 0 30 56 1 0 33 57 1 0 35 58 1 0 36 59 1 0 38 60 1 0 39 61 1 0 40 62 1 0 M END

Standard InCHIKey	KVPJDVHJFGPPAB-AXRGIPJOSA-N
Standard InCHI	InChI=1S/C30H22O10/c31-16-5-1-14(2-6-16)22-10-9-19-20(34)13-24-26(27(19)38-22)29(37)28(36)25-21(35)11-18(33)12-23(25)39-30(29,40-24)15-3-7-17(32)8-4-15/h1-8,11-13,22,31-35,37H,9-10H2/t22-,29-,30-/m0/s1
SMILES	Oc1ccc(cc1)[C@@H]1CCc2c(O1)c1c(cc2O)O[C@]2([C@@]1(O)C(=O)c1c(O)cc(cc1O2)O)c1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	542.12	Volume:	521.169 ? Van der Waals volume.
Dense:	1.04	LogP:	2.718 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.404 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.845 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	38.0
TPSA:	166.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	7.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.218	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.387	Fsp³:	0.167
MCE-18:	138.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.961	Fluc inhibitor:	0.674 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.864 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.929 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.306	Promiscuous compounds:	0.04

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.019	MDCK Permeability:	-4.878
Pgp-inhibitor:	0.005	Pgp-substrate:	0.982
PAMPA:	0.058 ? 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%):	0.048	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.988
Plasma Protein Binding (PPB):	94.762%	Volume Distribution (VD):	0.272
Fu:	7.085% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.915
OATP1B3 inhibitor:	0.91	BCRP inhibitor:	0.988
BSEP inhibitor:	0.973

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.039	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.988	CYP2D6-substrate:	0.009
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.368
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.101 ? 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):

5.582

Half-life (T1/2):

2.046

ADMET: Toxicity

hERG Blockers:	0.1	hERG Blockers (10um):	0.076
Human Hepatotoxicity (H-HT):	0.992	Drug-induced Liver Injury (DILI):	0.084
AMES Toxicity:	0.603	Rat Oral Acute Toxicity:	0.891
Maximum Recommended Daily Dose:	0.998	Skin Sensitization:	0.998
Carcinogencity:	0.716	Eye Corrosion:	0.0
Eye Irritation:	0.041	Respiratory Toxicity:	0.273
Drug-induced Neurotoxicity:	0.175	Ototoxicity:	0.716
Hematotoxicity:	0.028	Drug-induced Nephrotoxicity:	0.84
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.719
A549 Cytotoxicity:	0.992	Hek293 Cytotoxicity:	0.999
BCF:	1.371 ? 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:	4.299 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.309 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.778 ? 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
NPO19803	Oxytropis ochrocephala	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22494026]
NPO14508	Aconitum heterophyllum	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[24156713]
NPO4035	Daphne odora	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32997496]
NPO19303	Auricularia auricula-judae	Species	Auriculariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12444	Astragalus sinicus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19479	Trametes feei	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18393	Eugenia sandwicensis	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19803	Oxytropis ochrocephala	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14508	Aconitum heterophyllum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16416	Serratula strangulata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17135	Mikania goyazensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18816	Lindera glauca	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4035	Daphne odora	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19303	Auricularia auricula-judae	Species	Auriculariaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO18816	Lindera glauca	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14508	Aconitum heterophyllum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19303	Auricularia auricula-judae	Species	Auriculariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4035	Daphne odora	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12444	Astragalus sinicus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14508	Aconitum heterophyllum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16416	Serratula strangulata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12444	Astragalus sinicus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19303	Auricularia auricula-judae	Species	Auriculariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18393	Eugenia sandwicensis	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18816	Lindera glauca	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4035	Daphne odora	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4035	Daphne odora	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12444	Astragalus sinicus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16416	Serratula strangulata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4035	Daphne odora	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15287	Vernonia megapotamica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10882	Acer caudatifolium	Species	Aceraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12444	Astragalus sinicus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17558	Cynoglossum formosanum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7037	Rumohra adiantiformis	Species	Dryopteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18393	Eugenia sandwicensis	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17135	Mikania goyazensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14508	Aconitum heterophyllum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19406	Chrysanthemum leptophyllum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13505	Grateloupia livida	Species	Halymeniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19479	Trametes feei	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14015	Salacia cordata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10705	Marshallia graminifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12376	Baccharis macraei	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19803	Oxytropis ochrocephala	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18816	Lindera glauca	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19303	Auricularia auricula-judae	Species	Auriculariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18247	Globicephala melas	Species	Delphinidae	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
IC50	3

Activity Type	# Activity
Organism	2
Others	1

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
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	66680.0	nM	PMID[24530004]
NPT757	Organism	Plasmodium falciparum 3D7	Plasmodium falciparum 3D7	IC50	=	60580.0	nM	PMID[24530004]
NPT2	Others	Unspecified	n.a.	IC50	=	5230.0	nM	PMID[24530004]

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 NPC287884 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	27293
0.1-0.2	20129
0.2-0.3	1926
0.3-0.4	476
0.4-0.5	30
0.5-0.6	3
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC8704
0.5696	Remote Similarity	NPC82330
0.5147	Remote Similarity	NPC482472
0.507	Remote Similarity	NPC17809

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC287884 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5181
0.1-0.2	3934
0.2-0.3	24
0.3-0.4	10
0.4-0.5	1
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