NPASS Compound

Natural Product: NPC200412

Natural Product ID	NPC200412
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1R,3'r,4R,6S,7R,11Z)-7-Hydroxy-3',6,7,14-Tetramethylspiro[2,9-Dioxa-14-Azabicyclo[9.5.1]Heptadec-11-Ene-4,2'-Oxirane]-3,8,17-Trione
IUPAC Name	(1R,3'R,4R,6S,7R,11Z)-7-hydroxy-3',6,7,14-tetramethylspiro[2,9-dioxa-14-azabicyclo[9.5.1]heptadec-11-ene-4,2'-oxirane]-3,8,17-trione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1512570
PubChem CID	7566707
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000130] Azaspirodecane 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 54 56 0 0 0 0 0 0 0 0999 V2000 -4.2113 -0.1698 -0.8442 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7718 -0.5056 -0.5968 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2868 0.2065 0.6168 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2623 1.7193 0.4866 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2429 2.5654 0.8924 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0036 4.0538 1.0916 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2282 2.2218 -0.5227 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8800 2.1335 0.0824 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7195 3.2912 -0.4446 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2133 1.4548 0.1962 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4361 1.0364 0.1749 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6012 1.7913 -0.4193 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7578 0.8696 -0.7517 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2546 0.0475 0.2705 N 0 0 0 0 0 0 0 0 0 0 0 0 5.4366 0.5261 0.9431 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5077 -1.3605 -0.0802 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2137 -2.0982 0.1738 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9435 -1.6063 0.1192 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0593 -2.5637 0.8095 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3081 -2.2686 0.6688 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0642 -2.3359 -0.4657 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4336 -2.7455 -1.5113 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4892 -1.9978 -0.6143 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3377 -2.7538 0.3632 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8758 -2.4066 -1.9214 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5606 -0.3492 -0.4557 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2902 -0.3521 -1.6222 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7841 -1.0791 -1.1557 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7148 0.3137 0.0200 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2976 0.5246 -1.7016 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1806 -0.0739 -1.4636 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2578 -0.1450 0.9179 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9467 -0.0211 1.4761 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2056 2.2443 1.3295 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9608 4.2524 1.4237 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6656 4.4926 1.8547 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1690 4.6307 0.1586 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7850 0.9219 1.2789 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2517 2.2788 -1.3461 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9308 2.5848 0.2744 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5262 0.2910 -1.6686 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5954 1.5602 -1.0720 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0263 1.2388 0.3487 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1485 0.9964 1.9202 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1380 -0.2989 1.2254 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3087 -1.7933 0.5268 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6734 -1.4255 -1.1728 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2548 -3.1140 0.4288 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2670 -3.5949 0.4620 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2779 -2.5490 1.9134 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7365 -3.1358 1.2267 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8553 -3.6255 -0.1010 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1515 -2.1210 0.8019 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4174 -1.7568 -2.5215 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 5 7 1 0 4 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 17 18 2 3 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 23 25 1 6 18 26 1 0 26 27 2 0 23 2 1 0 4 7 1 6 26 11 1 0 1 28 1 0 1 29 1 0 1 30 1 0 2 31 1 6 3 32 1 0 3 33 1 0 5 34 1 1 6 35 1 0 6 36 1 0 6 37 1 0 11 38 1 1 12 39 1 0 12 40 1 0 13 41 1 0 13 42 1 0 15 43 1 0 15 44 1 0 15 45 1 0 16 46 1 0 16 47 1 0 17 48 1 0 19 49 1 0 19 50 1 0 24 51 1 0 24 52 1 0 24 53 1 0 25 54 1 0 M END

Standard InCHIKey	CZQLULNMKQAIQL-DCEQPIPLSA-N
Standard InCHI	InChI=1S/C19H27NO7/c1-11-9-19(12(2)27-19)17(23)26-14-6-8-20(4)7-5-13(15(14)21)10-25-16(22)18(11,3)24/h5,11-12,14,24H,6-10H2,1-4H3/b13-5-/t11-,12+,14+,18+,19+/m0/s1
SMILES	C[C@H]1C[C@@]2([C@@H](C)O2)C(=O)O[C@@H]2CCN(C)CC=C(COC(=O)[C@]1(C)O)C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	381.18	Volume:	373.493 ? Van der Waals volume.
Dense:	1.021	LogP:	0.316 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.696 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.848 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	24.0
TPSA:	105.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.469	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.281	Fsp³:	0.737
MCE-18:	82.939 ? 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:	0.247	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.013	Promiscuous compounds:	0.658

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.219	MDCK Permeability:	-4.881
Pgp-inhibitor:	0.009	Pgp-substrate:	0.553
PAMPA:	0.948 ? 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):	0.004
20% Bioavailability (F20%):	0.51	30% Bioavailability (F30%):	0.655
50% Bioavailability (F50%):	0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.149	MRP1:	0.992
Plasma Protein Binding (PPB):	31.652%	Volume Distribution (VD):	0.132
Fu:	66.528% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.979
OATP1B3 inhibitor:	0.954	BCRP inhibitor:	0.012
BSEP inhibitor:	0.606

ADMET: Metabolism

CYP1A2-inhibitor:	0.993	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.984	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.008	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.304	CYP3A4-substrate:	0.137
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.009
HLM stability:	0.598 ? 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):

5.065

Half-life (T1/2):

4.009

ADMET: Toxicity

hERG Blockers:	0.083	hERG Blockers (10um):	0.274
Human Hepatotoxicity (H-HT):	0.95	Drug-induced Liver Injury (DILI):	0.9
AMES Toxicity:	0.983	Rat Oral Acute Toxicity:	0.882
Maximum Recommended Daily Dose:	0.944	Skin Sensitization:	1.0
Carcinogencity:	0.995	Eye Corrosion:	0.012
Eye Irritation:	0.078	Respiratory Toxicity:	0.495
Drug-induced Neurotoxicity:	0.973	Ototoxicity:	0.352
Hematotoxicity:	0.819	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.368
A549 Cytotoxicity:	0.728	Hek293 Cytotoxicity:	0.745
BCF:	0.403 ? 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:	3.02 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.363 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.643 ? 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
NPO15275	Briareum asbestinum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12662092]
NPO1396	Cladogynos orientalis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[15679308]
NPO15275	Briareum asbestinum	Species	Briareidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[1686898]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21226514]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	stem	n.a.	PMID[21226514]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21226514]
NPO25140	Sapium sebiferum	Species	Euphorbiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[26281591]
NPO25140	Sapium sebiferum	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3404159]
NPO25140	Sapium sebiferum	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37988956]
NPO8306	Berneuxia thibetica	Species	Diapensiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1049	Tethya amamensis	Species	Tethyidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25140	Sapium sebiferum	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7793	Matricaria matricarioides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO117	Acacia armata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5166	Adonis sutchuenensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO643	Astragalus ernestii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1706	Eragrostis curvula	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8950	Stilpnopappus pickelii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1203	Solanum pseudoquina	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4836	Sideritis arborescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2323	Plantago lundborgii	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19991	Mantella aurantiaca	Species	Mantellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13682	Lonchocarpus laxiflorus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5339	Isophysis tasmanica	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8132	Fritillaria meleagris	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2008	Streptomyces ehimensis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17179	Elizabethkingia meningoseptica	Species	Flavobacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3445	Dumoria heckeli	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1541	Clusia ellipticifolia	Species	Clusiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1396	Cladogynos orientalis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21493	Bunodosoma caissarum	Species	Actiniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15275	Briareum asbestinum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8433	Bongardia chrysogonum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota	Pt	n.a.	n.a.	Database[FooDB]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5166	Adonis sutchuenensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25140	Sapium sebiferum	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8306	Berneuxia thibetica	Species	Diapensiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5166	Adonis sutchuenensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8306	Berneuxia thibetica	Species	Diapensiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO15275	Briareum asbestinum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2323	Plantago lundborgii	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19991	Mantella aurantiaca	Species	Mantellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7793	Matricaria matricarioides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1049	Tethya amamensis	Species	Tethyidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21493	Bunodosoma caissarum	Species	Actiniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8950	Stilpnopappus pickelii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO1706	Eragrostis curvula	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13682	Lonchocarpus laxiflorus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5166	Adonis sutchuenensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1541	Clusia ellipticifolia	Species	Clusiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17179	Elizabethkingia meningoseptica	Species	Flavobacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO10980	Petasites japonicus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25140	Sapium sebiferum	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5339	Isophysis tasmanica	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1203	Solanum pseudoquina	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8433	Bongardia chrysogonum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO117	Acacia armata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8132	Fritillaria meleagris	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2008	Streptomyces ehimensis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO1396	Cladogynos orientalis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4836	Sideritis arborescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO643	Astragalus ernestii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8306	Berneuxia thibetica	Species	Diapensiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6741	Metasequoia glyptostroboides	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3445	Dumoria heckeli	n.a.	n.a.	n.a.	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	3

Activity Type	# Activity
Individual protein	2
Protein-protein interaction	1

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	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT197	Protein-protein interaction	Menin/Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set

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 NPC200412 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	17320
0.1-0.2	31188
0.2-0.3	1318
0.3-0.4	22
0.4-0.5	2
0.5-0.6	2
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	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC156336
1.0	High Similarity	NPC120599
0.7143	Intermediate Similarity	NPC195435
0.7143	Intermediate Similarity	NPC196073
0.6818	Remote Similarity	NPC474497
0.6269	Remote Similarity	NPC275100
0.5571	Remote Similarity	NPC23963
0.5352	Remote Similarity	NPC609642

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC200412 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5071
0.1-0.2	4006
0.2-0.3	72
0.3-0.4	1
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