NPASS Compound

Natural Product: NPC177962

Natural Product ID	NPC177962
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(3,7-Dimethyl-9-((1S,4As,8As)-2,5,5,8A-Tetramethyl-1,4,4A,5,6,7,8,8A-Octahydronaphthalen-1-Yl)Nona-2,7-Dienyl)Benzene-1,4-Diol
IUPAC Name	2-[(2E,7E)-9-[(1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,6,7,8-hexahydronaphthalen-1-yl]-3,7-dimethylnona-2,7-dienyl]benzene-1,4-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL484372
PubChem CID	44588852
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001552] Sesterterpenoids

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 79 81 0 0 0 0 0 0 0 0999 V2000 0.3400 -0.2633 1.3475 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3277 -1.2340 0.2215 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6783 -1.1627 -0.6404 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7312 -0.1488 -0.4662 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1265 -0.6958 -0.3373 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3526 -1.6101 0.7795 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4371 -1.5579 1.5427 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5534 -0.5911 1.3818 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4414 -0.0621 -0.0319 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0532 0.5037 -0.1888 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5962 1.2517 1.0410 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0520 1.4288 -1.3571 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9002 2.6379 -0.9551 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2482 2.2789 -0.4485 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5501 0.8142 -0.4639 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7472 0.5680 0.4382 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0102 0.4685 -1.8865 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3720 -2.6902 1.1263 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3893 -2.2684 0.0877 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7692 -1.7544 -0.1547 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3467 -0.8505 0.8648 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7692 -0.4446 0.5008 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7095 -0.7637 1.3376 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1414 -0.5219 1.2793 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7844 0.1889 0.2119 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5134 -0.5214 -0.7258 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1795 0.1060 -1.7457 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9172 -0.6393 -2.6920 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1175 1.4766 -1.8329 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4017 2.2260 -0.9183 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7453 1.5592 0.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0268 2.3530 1.0077 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0344 0.2765 -0.7496 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0324 -0.6012 2.1533 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5272 0.7402 0.9607 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6626 -0.2069 1.8738 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7374 -1.8429 -1.4740 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5069 0.6079 0.3111 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7411 0.3843 -1.4855 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3633 -1.1720 -1.3138 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5713 -2.2678 2.3806 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4880 0.1618 2.1627 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5123 -1.1405 1.5021 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4782 -0.9767 -0.6966 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1289 0.5871 1.7929 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4259 1.7765 1.5545 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8582 2.0389 0.7804 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0657 1.8781 -1.6037 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5314 0.9822 -2.2365 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9045 3.3225 -1.8339 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3682 3.2307 -0.1549 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0037 2.7688 -1.1303 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4857 2.7220 0.5617 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1130 -0.4727 0.3249 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5669 1.2310 0.0347 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5851 0.8771 1.4777 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4537 -0.4466 -2.2263 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0769 0.1922 -1.9232 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8801 1.3228 -2.5765 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9294 -3.5640 1.5773 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7398 -2.3233 1.9433 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8611 -3.1138 0.2602 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0693 -2.9827 -0.7028 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4376 -2.8785 1.0330 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4068 -2.6595 -0.3460 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7074 -1.1609 -1.1188 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8241 0.1504 0.9022 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2993 -1.2879 1.8513 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3696 -1.3273 2.2780 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6894 -1.5236 1.4934 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4550 0.0399 2.2465 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5658 -1.6130 -0.6601 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4197 -1.0551 -3.4792 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6582 1.9548 -2.6573 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3768 3.3153 -1.0222 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4524 2.5668 1.9194 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0461 1.3837 -0.5843 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1640 0.1638 -1.4694 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8749 -0.1391 -1.2856 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 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 1 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 15 17 1 0 6 18 1 0 2 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 27 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 22 33 1 0 10 5 1 0 31 25 1 0 15 9 1 0 1 34 1 0 1 35 1 0 1 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 5 40 1 6 7 41 1 0 8 42 1 0 8 43 1 0 9 44 1 6 11 45 1 0 11 46 1 0 11 47 1 0 12 48 1 0 12 49 1 0 13 50 1 0 13 51 1 0 14 52 1 0 14 53 1 0 16 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 17 58 1 0 17 59 1 0 18 60 1 0 18 61 1 0 18 62 1 0 19 63 1 0 19 64 1 0 20 65 1 0 20 66 1 0 21 67 1 0 21 68 1 0 23 69 1 0 24 70 1 0 24 71 1 0 26 72 1 0 28 73 1 0 29 74 1 0 30 75 1 0 32 76 1 0 33 77 1 0 33 78 1 0 33 79 1 0 M END

Standard InCHIKey	FBBXOWQBMFRXRO-PGGDNBTOSA-N
Standard InCHI	InChI=1S/C31H46O2/c1-22(11-14-25-21-26(32)15-17-28(25)33)9-7-10-23(2)12-16-27-24(3)13-18-29-30(4,5)19-8-20-31(27,29)6/h11-13,15,17,21,27,29,32-33H,7-10,14,16,18-20H2,1-6H3/b22-11+,23-12+/t27-,29-,31+/m0/s1
SMILES	C/C(=CC[C@H]1C(=CC[C@@H]2[C@]1(C)CCCC2(C)C)C)/CCC/C(=C/Cc1cc(O)ccc1O)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	450.35	Volume:	520.824 ? Van der Waals volume.
Dense:	0.865	LogP:	8.457 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	5.073 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.909 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	19.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.306	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.15	Fsp³:	0.613
MCE-18:	76.36 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.98	Fluc inhibitor:	0.143 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.144 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.596	Promiscuous compounds:	0.262

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.901	MDCK Permeability:	-4.833
Pgp-inhibitor:	0.845	Pgp-substrate:	0.0
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):	0.001
20% Bioavailability (F20%):	0.988	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.07
Plasma Protein Binding (PPB):	96.96%	Volume Distribution (VD):	0.347
Fu:	2.806% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.561
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.988	CYP2C9-substrate:	0.997
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

11.142

Half-life (T1/2):

0.683

ADMET: Toxicity

hERG Blockers:	0.19	hERG Blockers (10um):	0.716
Human Hepatotoxicity (H-HT):	0.762	Drug-induced Liver Injury (DILI):	0.441
AMES Toxicity:	0.088	Rat Oral Acute Toxicity:	0.63
Maximum Recommended Daily Dose:	0.903	Skin Sensitization:	0.977
Carcinogencity:	0.303	Eye Corrosion:	0.0
Eye Irritation:	0.252	Respiratory Toxicity:	0.945
Drug-induced Neurotoxicity:	0.23	Ototoxicity:	0.611
Hematotoxicity:	0.322	Drug-induced Nephrotoxicity:	0.721
Genotoxicity:	0.801	RPMI-8226 Immunitoxicity:	0.104
A549 Cytotoxicity:	0.903	Hek293 Cytotoxicity:	0.917
BCF:	2.525 ? 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:	6.338 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.538 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.64 ? 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
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11374954]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15921404]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1593283]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18198840]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	at 1020 m depth from Chuuk Atoll, Federated States of Micronesia	n.a.	PMID[18824352]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20230038]
NPO30318	Coscinoderma	Genus	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21827183]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[26551342]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[26863083]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[27336796]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[32243140]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	Indo-Pacific	n.a.	PMID[7494145]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9748373]

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	5
MIC	16

Activity Type	# Activity
Individual protein	3
Organism	17
Protein complex	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1087	Individual protein	Isocitrate lyase	Candida albicans	IC50	=	76800.0	nM	PMID[18824352]
NPT1821	Individual protein	Sortase	Staphylococcus aureus	IC50	>	200000.0	nM	PMID[21827183]
NPT1087	Individual protein	Isocitrate lyase	Candida albicans	IC50	>	200000.0	nM	PMID[21827183]
NPT2890	Protein complex	Sodium/potassium-transporting ATPase	Homo sapiens	IC50	=	117000.0	nM	PMID[21827183]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	25.0	ug.mL-1	PMID[18824352]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	25.0	ug.mL-1	PMID[18824352]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT20	Organism	Candida albicans	Candida albicans	IC50	=	222200.0	nM	PMID[18824352]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	3.25	ug.mL-1	PMID[18824352]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT329	Organism	Trichophyton rubrum	Trichophyton rubrum	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT330	Organism	Trichophyton mentagrophytes	Trichophyton mentagrophytes	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	100.0	ug.mL-1	PMID[21827183]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	=	6.25	ug.mL-1	PMID[18824352]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	>	100.0	ug.mL-1	PMID[21827183]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	MIC	>	100.0	ug.mL-1	PMID[21827183]

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 NPC177962 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	16514
0.1-0.2	31458
0.2-0.3	1754
0.3-0.4	110
0.4-0.5	8
0.5-0.6	10
0.6-0.7	2
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	NPC62867
0.6986	Remote Similarity	NPC325544
0.68	Remote Similarity	NPC477037
0.5781	Remote Similarity	NPC320439
0.5769	Remote Similarity	NPC323074
0.5606	Remote Similarity	NPC155072
0.5357	Remote Similarity	NPC329685
0.5246	Remote Similarity	NPC260775
0.5246	Remote Similarity	NPC130756
0.5246	Remote Similarity	NPC70677
0.5246	Remote Similarity	NPC12931
0.5176	Remote Similarity	NPC318581
0.5167	Remote Similarity	NPC152097

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC177962 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6372
0.1-0.2	2745
0.2-0.3	33
0.3-0.4	0
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