NPASS Compound

Natural Product: NPC551458

Natural Product ID	NPC551458
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},15~{R},16~{R},18~{S})-15,16-dihydroxy-5',7,9,13-tetramethyl-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-10-one
IUPAC Name	(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},15~{R},16~{R},18~{S})-15,16-dihydroxy-5',7,9,13-tetramethyl-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-10-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 74 79 0 0 0 0 0 0 0 0999 V2000 7.7128 1.7700 0.9953 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6560 1.0205 0.2308 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9970 1.9208 -0.8110 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9470 1.1001 -1.4989 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9735 0.5974 -0.4831 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5360 -0.0684 0.5740 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5610 0.6031 1.1918 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0842 1.6033 -0.1023 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9549 1.0285 0.3893 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6674 1.5377 -0.2902 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1970 0.3864 0.0922 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6196 0.4180 -0.1164 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2071 0.4677 -1.4593 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6784 0.8914 -1.2850 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2264 0.4378 0.0335 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.7261 0.2380 -0.1591 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3343 0.0576 1.1886 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.3770 -0.8958 1.1491 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3727 -0.2158 2.2885 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9686 0.9895 2.9101 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2190 -1.0786 1.9345 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6596 -0.8424 0.5480 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1897 -1.9973 -0.3124 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1843 -0.8051 0.6243 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5138 -2.0887 0.1858 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0437 -1.9652 0.1812 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6464 -2.8057 0.6930 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5690 -0.7845 -0.4666 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4328 -0.9783 -1.9453 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9562 -0.4537 -0.0280 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9742 -0.3758 -1.1406 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6943 -1.6420 -1.4096 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7093 1.3127 0.8396 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7703 2.8229 0.6773 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5106 1.7465 2.0795 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0419 0.1204 -0.2552 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4883 2.7525 -0.2707 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7497 2.3430 -1.4808 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3787 0.3198 -2.1436 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3746 1.7920 -2.1830 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1762 1.4538 1.7869 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0385 -0.0992 1.9162 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8754 1.1445 1.4731 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3836 2.4812 0.2179 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8391 1.6448 -1.3634 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0406 0.2840 1.2181 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0393 1.2876 0.4696 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7612 1.2491 -2.1030 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2799 -0.5035 -2.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3001 0.4876 -2.1245 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7757 1.9945 -1.3550 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1223 1.2735 0.7513 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9504 -0.5695 -0.8807 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0779 1.1824 -0.6673 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8610 1.0248 1.4421 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1645 -0.6056 1.6505 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9496 -0.7522 3.1012 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5307 1.7481 2.6365 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5152 -2.1591 2.0788 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4200 -0.9126 2.6984 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2356 -1.7423 -1.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2316 -2.2276 0.0611 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6214 -2.9411 -0.0982 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8517 -0.6472 1.6934 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8154 -2.3664 -0.8448 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8041 -2.8609 0.9105 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2930 -1.8071 -2.2075 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2831 -0.0702 -2.5285 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4099 -1.4244 -2.3052 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3622 -1.0895 0.7563 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6195 0.1770 -2.0319 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1786 -2.5409 -1.0360 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8875 -1.7283 -2.5075 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7185 -1.6656 -0.9395 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 1 6 7 1 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 22 23 1 6 22 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 6 28 30 1 0 30 31 1 0 31 32 1 0 7 2 1 0 30 9 1 0 31 5 1 0 28 11 1 0 24 12 1 0 22 15 1 0 1 33 1 0 1 34 1 0 1 35 1 0 2 36 1 6 3 37 1 0 3 38 1 0 4 39 1 0 4 40 1 0 7 41 1 0 7 42 1 0 9 43 1 1 10 44 1 0 10 45 1 0 11 46 1 1 12 47 1 1 13 48 1 0 13 49 1 0 14 50 1 0 14 51 1 0 15 52 1 1 16 53 1 0 16 54 1 0 17 55 1 1 18 56 1 0 19 57 1 1 20 58 1 0 21 59 1 0 21 60 1 0 23 61 1 0 23 62 1 0 23 63 1 0 24 64 1 1 25 65 1 0 25 66 1 0 29 67 1 0 29 68 1 0 29 69 1 0 30 70 1 1 31 71 1 6 32 72 1 0 32 73 1 0 32 74 1 0 M END

Standard InCHIKey	PBLXVDNSLUFVHF-GZSNWLOUSA-N
Standard InCHI	InChI=1S/C27H42O5/c1-14-7-8-27(31-13-14)15(2)24-22(32-27)10-19-17-6-5-16-9-20(28)21(29)12-25(16,3)18(17)11-23(30)26(19,24)4/h14-22,24,28-29H,5-13H2,1-4H3/t14-,15+,16+,17+,18+,19+,20-,21-,22+,24+,25+,26-,27-/m1/s1
SMILES	C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@H]4CC[C@H]5C[C@@H](O)[C@H](O)C[C@]5(C)[C@H]4CC(=O)[C@]3(C)[C@H]1[C@@H]2C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	446.3	Volume:	465.524 ? Van der Waals volume.
Dense:	0.959	LogP:	3.823 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.873 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.775 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	31.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.589	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.551	Fsp³:	0.963
MCE-18:	145.547 ? 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:	0.69	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.024 ? 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:	0.166	Promiscuous compounds:	0.795

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.957	MDCK Permeability:	-4.806
Pgp-inhibitor:	0.224	Pgp-substrate:	0.129
PAMPA:	0.397 ? 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%):	0.171	30% Bioavailability (F30%):	0.475
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.066	MRP1:	0.178
Plasma Protein Binding (PPB):	85.445%	Volume Distribution (VD):	0.077
Fu:	18.412% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.925
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.007
CYP2C19-inhibitor:	0.174	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.159
CYP3A4-inhibitor:	0.974	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.99 ? 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):

15.3

Half-life (T1/2):

2.03

ADMET: Toxicity

hERG Blockers:	0.147	hERG Blockers (10um):	0.45
Human Hepatotoxicity (H-HT):	0.595	Drug-induced Liver Injury (DILI):	0.747
AMES Toxicity:	0.415	Rat Oral Acute Toxicity:	0.205
Maximum Recommended Daily Dose:	0.51	Skin Sensitization:	0.988
Carcinogencity:	0.569	Eye Corrosion:	0.004
Eye Irritation:	0.236	Respiratory Toxicity:	0.209
Drug-induced Neurotoxicity:	0.056	Ototoxicity:	0.825
Hematotoxicity:	0.14	Drug-induced Nephrotoxicity:	0.526
Genotoxicity:	0.005	RPMI-8226 Immunitoxicity:	0.135
A549 Cytotoxicity:	0.343	Hek293 Cytotoxicity:	0.694
BCF:	2.135 ? 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:	3.884 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.172 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.648 ? 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
NPO16699	Agave utahensis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19645463]
NPO62863	Agave parassanas	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47407	Agave bracteosa Wats.	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1530	Agave cantala	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO55167	Agave chisoensis	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO60193	Agave crassipina	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7928	Agave east-one	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO56749	Agave ferox	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53843	Agave havardiana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52574	Agave lehmannii	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2081	Agave lophantha	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO55410	Agave mirabilis	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47190	Agave mitraeformis	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7830	Agave angustifolia	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO57883	Agave quoitefera	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO44746	Agave roezliana	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO54412	Agave salmiana Otto.	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO46487	Agave scabra	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52698	Agave striata Zucc.	Genus	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47212	Maguey canasto	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52259	Maguey cenisto	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO49264	Maguey cimmaron	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62246	Maguey cochabamba	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14537	Manfreda tigrina	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42563	Samuela carnoserana	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7564	Manfreda maculosa	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29139	Agave huachucensis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16699	Agave utahensis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7842	Agave atrovirens	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7928	Agave east-one	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7830	Agave angustifolia	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1530	Agave cantala	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7928	Agave east-one	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7830	Agave angustifolia	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1530	Agave cantala	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7830	Agave angustifolia	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14537	Manfreda tigrina	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7830	Agave angustifolia	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29139	Agave huachucensis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7842	Agave atrovirens	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1530	Agave cantala	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7564	Manfreda maculosa	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2081	Agave lophantha	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16699	Agave utahensis	Species	Asparagaceae	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 NPC551458 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	23106
0.1-0.2	25738
0.2-0.3	845
0.3-0.4	120
0.4-0.5	37
0.5-0.6	9
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
0.7727	Intermediate Similarity	NPC161035
0.7727	Intermediate Similarity	NPC170438
0.746	Intermediate Similarity	NPC227260
0.5857	Remote Similarity	NPC273290
0.5857	Remote Similarity	NPC232044
0.5714	Remote Similarity	NPC248944
0.5714	Remote Similarity	NPC7479
0.5714	Remote Similarity	NPC257296
0.5444	Remote Similarity	NPC215408
0.5352	Remote Similarity	NPC24556
0.5158	Remote Similarity	NPC202898
0.5052	Remote Similarity	NPC92890

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC551458 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7056
0.1-0.2	2039
0.2-0.3	49
0.3-0.4	2
0.4-0.5	3
0.5-0.6	1
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
0.5714	Remote Similarity	NPD6928	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