NPASS Compound

Natural Product: NPC116123

Natural Product ID	NPC116123
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FNCKOVJIJVZKHE-OIPWLAMZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	21573749
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0002724] Steroidal alkaloids [CHEMONTID:0002731] Conanine-type alkaloids

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 56 60 0 0 0 0 0 0 0 0999 V2000 -5.0337 -0.3290 -0.9310 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6879 -0.7711 -0.4783 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5468 -0.1232 -1.2295 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6910 1.3813 -1.1658 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3717 1.9194 -0.5961 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4844 0.7571 -0.6821 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7093 0.7412 0.2238 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4257 2.0302 0.2970 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5895 1.8824 1.2912 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4449 0.8266 0.6164 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6527 1.1373 0.2453 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5592 0.2104 -0.4163 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7256 0.5061 -0.7741 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0438 -1.1246 -0.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8055 -1.4010 -0.2601 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8780 -0.5061 0.4104 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7475 -1.0922 1.8485 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5336 -0.4591 -0.2381 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6833 -1.6672 0.0940 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6328 -1.6660 -0.6668 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3777 -0.4004 -0.3470 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9565 -0.3588 1.0229 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3981 -0.5587 0.8960 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.1679 0.4431 1.5488 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3010 -2.8709 -0.1513 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2598 -0.8852 -1.8885 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7829 -0.6865 -0.2074 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1245 0.7331 -1.1803 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5982 -1.8774 -0.6770 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4436 -0.5008 -2.2598 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8374 1.7367 -2.2133 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4784 1.7248 -0.4965 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5122 2.3456 0.4153 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0549 2.7310 -1.2544 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1367 0.6223 -1.7235 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3434 0.4621 1.2499 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7238 2.8052 0.6111 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8556 2.2574 -0.7037 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2195 1.4242 2.2139 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1134 2.8260 1.3713 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9997 2.1704 0.4504 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6646 -1.8817 -1.1555 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5236 -2.4531 -0.5023 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6768 -2.1925 1.7863 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9172 -0.6319 2.3787 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6807 -0.8676 2.4133 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6102 -0.3928 -1.3328 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3762 -1.5668 1.1787 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2285 -2.5079 -0.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4991 -1.7789 -1.7477 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7112 0.5412 1.6072 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5885 -1.2328 1.6128 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5572 1.3351 1.8702 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5239 0.0035 2.5270 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0694 0.7724 1.0269 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9506 -3.5419 0.5000 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 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 1 16 18 1 0 18 19 1 0 19 20 1 0 21 20 1 6 21 22 1 0 22 23 1 0 23 24 1 0 19 25 1 0 23 2 1 0 21 3 1 0 21 6 1 0 18 7 1 0 16 10 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 1 3 30 1 6 4 31 1 0 4 32 1 0 5 33 1 0 5 34 1 0 6 35 1 6 7 36 1 1 8 37 1 0 8 38 1 0 9 39 1 0 9 40 1 0 11 41 1 0 14 42 1 0 15 43 1 0 17 44 1 0 17 45 1 0 17 46 1 0 18 47 1 6 19 48 1 1 20 49 1 0 20 50 1 0 22 51 1 0 22 52 1 0 24 53 1 0 24 54 1 0 24 55 1 0 25 56 1 0 M END

Standard InCHIKey	FNCKOVJIJVZKHE-OIPWLAMZSA-N
Standard InCHI	InChI=1S/C22H31NO2/c1-13-17-6-7-18-16-5-4-14-10-15(24)8-9-21(14,2)20(16)19(25)11-22(17,18)12-23(13)3/h8-10,13,16-20,25H,4-7,11-12H2,1-3H3/t13-,16-,17+,18-,19+,20+,21-,22-/m0/s1
SMILES	C[C@H]1[C@H]2CC[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](C[C@]23CN1C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	341.24	Volume:	366.954 ? Van der Waals volume.
Dense:	0.93	LogP:	2.216 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.414 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.424 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	25.0
TPSA:	40.54 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.735	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.113	Fsp³:	0.773
MCE-18:	111.538 ? 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:	0.83	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.303 ? 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:	0.016	Promiscuous compounds:	0.372

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.922	MDCK Permeability:	-4.63
Pgp-inhibitor:	0.081	Pgp-substrate:	0.046
PAMPA:	0.04 ? 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%):	0.022	30% Bioavailability (F30%):	0.438
50% Bioavailability (F50%):	0.846

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	1.0	MRP1:	0.583
Plasma Protein Binding (PPB):	69.164%	Volume Distribution (VD):	0.523
Fu:	29.779% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.294
BSEP inhibitor:	0.693

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.951	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.232
CYP2D6-inhibitor:	0.505	CYP2D6-substrate:	0.065
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.007
HLM stability:	0.158 ? 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):

13.074

Half-life (T1/2):

1.832

ADMET: Toxicity

hERG Blockers:	0.184	hERG Blockers (10um):	0.428
Human Hepatotoxicity (H-HT):	0.668	Drug-induced Liver Injury (DILI):	0.188
AMES Toxicity:	0.388	Rat Oral Acute Toxicity:	0.823
Maximum Recommended Daily Dose:	0.929	Skin Sensitization:	0.98
Carcinogencity:	0.764	Eye Corrosion:	0.016
Eye Irritation:	0.715	Respiratory Toxicity:	0.96
Drug-induced Neurotoxicity:	0.543	Ototoxicity:	0.491
Hematotoxicity:	0.299	Drug-induced Nephrotoxicity:	0.367
Genotoxicity:	0.935	RPMI-8226 Immunitoxicity:	0.172
A549 Cytotoxicity:	0.108	Hek293 Cytotoxicity:	0.55
BCF:	1.028 ? 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:	3.705 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.322 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.669 ? 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
NPO4862	Westiellopsis prolifica	Species	Hapalosiphonaceae	Bacteria	n.a.	n.a.	n.a.	PMID[1602299]
NPO11532	Bidens parviflora	Species	Asteraceae	Eukaryota	n.a.	whole plant	n.a.	PMID[16880667]
NPO14386	Piper hostmannianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO10561	Mentha suaveolens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36432812]
NPO10561	Mentha suaveolens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37836777]
NPO10561	Mentha suaveolens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38560258]
NPO4862	Westiellopsis prolifica	Species	Hapalosiphonaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO765	Holarrhena pubescens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11073	Alpinia formosana	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21147	Anisocycla grandidieri	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13117	Asparagus setaceus	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3577	Bambusa tulda	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11532	Bidens parviflora	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9025	Croton balsamifer	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13993	Dimelaena thysanota	Species	Caliciaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14583	Elsholtzia stauntonii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14603	Flindersia australis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8641	Haemanthus tigrinus	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12589	Heliotropium angiospermum	Species	Heliotropiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10561	Mentha suaveolens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO805	Myrmicaria opaciventris	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1421	Papaver hybrid	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6627	Pinus bungeana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14386	Piper hostmannianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10834	Protea compacta	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11334	Rubus moluccanus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13898	Typhonium flagelliforme	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO765	Holarrhena pubescens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6627	Pinus bungeana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13117	Asparagus setaceus	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11532	Bidens parviflora	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO765	Holarrhena pubescens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10561	Mentha suaveolens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13117	Asparagus setaceus	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6627	Pinus bungeana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO765	Holarrhena pubescens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3577	Bambusa tulda	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6627	Pinus bungeana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14386	Piper hostmannianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14583	Elsholtzia stauntonii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13993	Dimelaena thysanota	Species	Caliciaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11532	Bidens parviflora	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12589	Heliotropium angiospermum	Species	Heliotropiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO805	Myrmicaria opaciventris	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13117	Asparagus setaceus	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14603	Flindersia australis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4862	Westiellopsis prolifica	Species	Hapalosiphonaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO765	Holarrhena pubescens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21147	Anisocycla grandidieri	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13898	Typhonium flagelliforme	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1421	Papaver hybrid	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8641	Haemanthus tigrinus	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11334	Rubus moluccanus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10561	Mentha suaveolens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10834	Protea compacta	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11073	Alpinia formosana	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9025	Croton balsamifer	Species	Euphorbiaceae	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 NPC116123 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	17420
0.1-0.2	31507
0.2-0.3	880
0.3-0.4	44
0.4-0.5	6
0.5-0.6	2
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	Natural Product ID
0.5441	Remote Similarity	NPC169375
0.5294	Remote Similarity	NPC334061

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC116123 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5255
0.1-0.2	3708
0.2-0.3	108
0.3-0.4	59
0.4-0.5	17
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5373	Remote Similarity	NPD6079	Phase 4
0.5294	Remote Similarity	NPD4696	Phase 4
0.5217	Remote Similarity	NPD5211	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