NPASS Compound

Natural Product: NPC126518

Natural Product ID	NPC126518
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Manoalide
IUPAC Name	(2R)-2-hydroxy-3-[(2R,6R)-6-hydroxy-5-[(E)-4-methyl-6-(2,6,6-trimethylcyclohexen-1-yl)hex-3-enyl]-3,6-dihydro-2H-pyran-2-yl]-2H-furan-5-one
Synonyms	Manoalide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL463914
PubChem CID	6437368
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 66 68 0 0 0 0 0 0 0 0999 V2000 -0.1531 -2.1938 -1.4490 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6943 -1.1202 -0.5922 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0763 -0.3334 0.0990 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5271 -0.2967 0.2130 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3528 -1.3842 -0.3558 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8179 -1.0636 -0.1286 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5559 -1.8884 0.5656 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0236 -1.6088 0.8175 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4096 -0.2980 0.1721 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7067 -0.0347 -0.9989 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3627 0.1736 -0.6968 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6669 0.5937 -1.8389 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1995 0.8694 1.0974 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7202 0.8633 2.3095 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7049 2.2273 2.8066 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3132 2.5960 3.9230 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2045 3.0324 1.8112 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5370 2.2364 0.7071 C 0 0 1 0 0 0 0 0 0 0 0 0 7.9101 2.3688 0.4644 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2042 -0.9583 -0.5415 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6662 0.1356 0.3421 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1529 0.2021 0.3260 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7488 -0.0279 1.5010 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0810 -0.3300 2.7544 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2564 0.0565 1.5087 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6572 1.2965 0.7213 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2885 1.0242 -0.6974 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8892 0.5145 -0.9170 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1725 1.6392 -1.6920 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9678 -0.6455 -1.8630 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2494 -1.7969 -2.4178 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4244 -2.9708 -0.9744 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0843 -2.7570 -1.8205 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4901 0.4521 0.7102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9298 0.7184 -0.1391 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7654 -0.2319 1.3370 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2808 -1.5425 -1.4356 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1274 -2.3107 0.2491 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1515 -2.8007 0.9877 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5760 -2.4061 0.3051 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2386 -1.6470 1.8823 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4924 -0.3067 -0.0972 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2181 0.9716 0.0636 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6938 -0.1093 -2.5329 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3856 0.0017 2.8678 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9501 2.5880 -0.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3214 1.4765 0.5313 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5755 -1.9618 -0.2567 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4803 -0.8205 -1.6062 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2849 0.0345 1.4001 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2287 1.1238 0.0031 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3802 -1.1859 2.7181 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8246 -0.5837 3.5328 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5679 0.6007 3.1145 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6625 0.1712 2.5162 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6172 -0.8594 1.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1731 2.1747 1.1559 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7675 1.3481 0.7745 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9979 0.2073 -1.0399 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5060 1.8864 -1.3647 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1111 1.4578 -1.8296 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2771 2.6021 -1.1472 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7129 1.7300 -2.6644 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4651 -0.4942 -2.8358 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0537 -0.7807 -2.1452 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7011 -1.6252 -1.3853 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 0 11 12 1 0 9 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 2 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 23 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 28 30 1 0 11 6 1 0 18 13 1 0 28 22 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 7 39 1 0 8 40 1 0 8 41 1 0 9 42 1 6 11 43 1 1 12 44 1 0 14 45 1 0 18 46 1 6 19 47 1 0 20 48 1 0 20 49 1 0 21 50 1 0 21 51 1 0 24 52 1 0 24 53 1 0 24 54 1 0 25 55 1 0 25 56 1 0 26 57 1 0 26 58 1 0 27 59 1 0 27 60 1 0 29 61 1 0 29 62 1 0 29 63 1 0 30 64 1 0 30 65 1 0 30 66 1 0 M END

Standard InCHIKey	FGJIDQWRRLDGDB-CPIXEKRISA-N
Standard InCHI	InChI=1S/C25H36O5/c1-16(10-12-20-17(2)8-6-14-25(20,3)4)7-5-9-18-11-13-21(29-23(18)27)19-15-22(26)30-24(19)28/h7,11,15,21,23-24,27-28H,5-6,8-10,12-14H2,1-4H3/b16-7+/t21-,23-,24-/m1/s1
SMILES	C/C(=CCCC1=CC[C@@H](O[C@H]1O)C1=CC(=O)O[C@H]1O)/CCC1=C(C)CCCC1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	416.26	Volume:	446.056 ? Van der Waals volume.
Dense:	0.933	LogP:	4.868 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.155 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.613 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	19.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.458	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.608	Fsp³:	0.64
MCE-18:	50.195 ? 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:	0.987	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.065 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.047 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.379	Promiscuous compounds:	0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.885	MDCK Permeability:	-4.713
Pgp-inhibitor:	0.526	Pgp-substrate:	0.283
PAMPA:	0.031 ? 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):	0.003
20% Bioavailability (F20%):	0.005	30% Bioavailability (F30%):	0.039
50% Bioavailability (F50%):	0.849

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.983
Plasma Protein Binding (PPB):	97.149%	Volume Distribution (VD):	0.376
Fu:	2.317% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.298
OATP1B3 inhibitor:	0.262	BCRP inhibitor:	0.001
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.029	CYP1A2-substrate:	0.052
CYP2C19-inhibitor:	0.451	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.16	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.446	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.018	CYP3A4-substrate:	0.315
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.193
HLM stability:	0.79 ? 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):

5.095

Half-life (T1/2):

0.994

ADMET: Toxicity

hERG Blockers:	0.048	hERG Blockers (10um):	0.285
Human Hepatotoxicity (H-HT):	0.663	Drug-induced Liver Injury (DILI):	0.345
AMES Toxicity:	0.61	Rat Oral Acute Toxicity:	0.392
Maximum Recommended Daily Dose:	0.969	Skin Sensitization:	0.986
Carcinogencity:	0.508	Eye Corrosion:	0.0
Eye Irritation:	0.076	Respiratory Toxicity:	0.719
Drug-induced Neurotoxicity:	0.323	Ototoxicity:	0.736
Hematotoxicity:	0.297	Drug-induced Nephrotoxicity:	0.912
Genotoxicity:	0.891	RPMI-8226 Immunitoxicity:	0.323
A549 Cytotoxicity:	0.135	Hek293 Cytotoxicity:	0.26
BCF:	2.034 ? 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:	4.895 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.482 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.015 ? 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
NPO5099	Luffariella variabilis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0040-4039(00)77766-5]
NPO12514	Fasciospongia cavernosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10514323]
NPO16746	Lendenfeldia frondosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1402955]
NPO32622	luffariella sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1624940]
NPO32622	luffariella sp.	Species	Thorectidae	Eukaryota	n.a.	Okinawan	n.a.	PMID[8482949]
NPO12514	Fasciospongia cavernosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8594155]
NPO12514	Fasciospongia cavernosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9677277]
NPO12514	Fasciospongia cavernosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16746	Lendenfeldia frondosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5099	Luffariella variabilis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO33053	laffaariella variabilis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[Title]
NPO16746	Lendenfeldia frondosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12514	Fasciospongia cavernosa	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5099	Luffariella variabilis	Species	Thorectidae	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	26
Inhibition	19
ED50	1

Activity Type	# Activity
Individual protein	38
Cell line	2
Organism	1
Single protein	1
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2945	Individual protein	Phospholipase A2 group 1B	Sus scrofa	Inhibition	=	32.3	%	PMID[11374954]
NPT3172	Individual protein	Phospholipase A2 group IIA	Homo sapiens	Inhibition	=	93.2	%	PMID[11374954]
NPT3172	Individual protein	Phospholipase A2 group IIA	Homo sapiens	IC50	=	3900.0	nM	PMID[9677277]
NPT3172	Individual protein	Phospholipase A2 group IIA	Homo sapiens	IC50	=	1500000.0	nM	PMID[8978846]
NPT2586	Individual protein	Phospholipase A2, acidic	Naja naja	Inhibition	=	17.0	%	PMID[11374954]
NPT2586	Individual protein	Phospholipase A2, acidic	Naja naja	IC50	=	17000.0	nM	PMID[9677277]
NPT3172	Individual protein	Phospholipase A2 group IIA	Homo sapiens	IC50	=	93200.0	nM	PMID[9677277]
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	IC50	=	5600.0	nM	PMID[27362876]
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	IC50	=	3400.0	nM	PMID[27362876]
NPT4421	Individual protein	Group IID secretory phospholipase A2	Homo sapiens	IC50	=	0.34	ug.mL-1	DOI[10.1016/0960-894X(95)00215-F]
NPT4425	Individual protein	Phospholipase A2 alpha	Crotalus adamanteus	IC50	=	400.0	nM	PMID[17190441]
NPT4062	Individual protein	Phospholipase A2 group IIA	Rattus norvegicus	IC50	=	2000000.0	nM	PMID[8978846]
NPT4423	Individual protein	Cytosolic phospholipase A2	Mus musculus	Inhibition	=	44.6	%	PMID[11374954]
NPT4062	Individual protein	Phospholipase A2 group IIA	Rattus norvegicus	IC50	=	38400.0	nM	PMID[9677277]
NPT545	Individual protein	Phospholipase A2 group 1B	Homo sapiens	Inhibition	=	17.0	%	PMID[9703468]
NPT545	Individual protein	Phospholipase A2 group 1B	Homo sapiens	IC50	=	3900.0	nM	PMID[9599251]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	62.5	%	PMID[11374954]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	IC50	=	7500.0	nM	PMID[9677277]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	42.4	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	21.0	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	49.5	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	44.2	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	28.0	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	63.3	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	47.3	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	43.1	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	91.1	%	PMID[9703468]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	IC50	=	62500.0	nM	PMID[9677277]
NPT24397	Single protein	Phospholipase A2	Apis mellifera	IC50	=	40.0	nM	PMID[1294693]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	IC50	=	500.0	nM	PMID[21256013]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT137	Cell line	L1210	Mus musculus	IC50	=	0.032	ug.mL-1	PMID[8482949]
NPT91	Cell line	KB	Homo sapiens	IC50	=	0.31	ug.mL-1	PMID[8482949]
NPT2	Others	Unspecified	n.a.	Inhibition	=	100.0	%	PMID[1402955]
NPT2	Others	Unspecified	n.a.	IC50	=	32300.0	nM	PMID[9677277]
NPT2	Others	Unspecified	n.a.	IC50	=	15000.0	nM	PMID[22394195]
NPT2	Others	Unspecified	n.a.	IC50	=	70000.0	nM	PMID[22394195]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	100.0	ug	PMID[8792625]

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 NPC126518 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	19677
0.1-0.2	27408
0.2-0.3	2655
0.3-0.4	81
0.4-0.5	19
0.5-0.6	12
0.6-0.7	1
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
0.717	Intermediate Similarity	NPC473756
0.7097	Intermediate Similarity	NPC163606
0.623	Remote Similarity	NPC209135
0.5968	Remote Similarity	NPC471298
0.5873	Remote Similarity	NPC323251
0.5781	Remote Similarity	NPC474865
0.5714	Remote Similarity	NPC211892
0.5714	Remote Similarity	NPC324170
0.5625	Remote Similarity	NPC471301
0.5455	Remote Similarity	NPC222244
0.5455	Remote Similarity	NPC16349
0.5441	Remote Similarity	NPC474816
0.541	Remote Similarity	NPC474860
0.5323	Remote Similarity	NPC471297
0.5152	Remote Similarity	NPC489320

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC126518 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7075
0.1-0.2	2042
0.2-0.3	31
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD6400	Clinical (unspecified phase)

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