NPASS Compound

Natural Product: NPC542823

Natural Product ID	NPC542823
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)chroman-4-one
IUPAC Name	(2~{S})-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)chroman-4-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 77 81 0 0 0 0 0 0 0 0999 V2000 8.5712 1.8224 -1.7278 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5604 0.6219 -1.0130 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3905 -0.1177 -0.9210 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2320 0.3212 -1.5347 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0548 -0.4107 -1.4493 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9957 -1.6077 -0.7464 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7347 -2.3520 -0.6752 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4622 -3.2254 -1.8486 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0340 -3.4504 -2.1338 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6940 -4.1767 -3.0952 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0126 -2.8492 -1.3252 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3202 -3.2292 -1.3659 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6614 -4.2480 -2.2440 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2751 -2.6432 -0.5870 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9503 -1.6114 0.3070 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9309 -1.0418 1.0782 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7370 -0.0046 1.9638 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8043 -0.5549 3.2532 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3122 0.4647 4.0890 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7558 -0.0709 5.3657 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2927 0.9825 6.1337 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4713 1.3987 4.2842 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2659 2.3264 5.2751 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8358 2.0279 2.9656 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1234 2.5752 3.1278 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7419 1.1218 1.7966 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4821 1.7301 0.5992 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4339 1.5581 -0.3748 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9251 0.8188 -1.4343 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9213 0.2140 -2.1895 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4724 0.0360 -3.6258 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2350 0.9423 -2.0963 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9637 0.6683 -3.2512 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0192 2.4384 -2.0023 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4719 2.8954 -3.2056 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1320 2.7987 -0.8302 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9772 3.2565 0.1850 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3777 -1.2433 0.3375 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3521 -1.8367 -0.4528 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6859 -1.4338 -0.3896 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1639 -2.0308 -0.1390 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3279 -1.3055 -0.2246 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4796 -1.7841 0.4113 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5047 1.7057 -2.8219 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4802 2.4311 -1.4814 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7146 2.4606 -1.3837 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2278 1.2516 -2.0955 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1476 -0.0591 -1.9359 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8114 -3.0102 0.2411 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9987 -2.8223 -2.7435 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9430 -4.2250 -1.6559 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2794 -5.1854 -2.1765 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3312 -2.9356 -0.6103 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7139 0.3897 1.8920 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4954 1.0041 3.5379 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1257 -0.6978 5.1157 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4972 -0.6417 5.9320 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6801 0.9337 6.3273 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3413 0.7559 4.6010 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0510 2.9081 5.3398 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1548 2.8966 2.8351 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6138 2.0035 3.7598 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7374 0.5991 1.6970 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2392 0.9101 0.0868 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0765 -0.8032 -1.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4342 1.0162 -4.1291 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4853 -0.4722 -3.6443 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1624 -0.6044 -4.2007 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8024 0.5510 -1.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8765 1.0923 -3.2124 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0214 2.8990 -1.8826 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1742 2.9923 -3.8964 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4303 3.5935 -1.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5699 4.1021 0.5276 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7373 -0.4428 1.0068 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1204 -2.9690 0.4124 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3794 -1.4181 0.1489 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 15 38 1 0 38 39 2 0 39 40 1 0 6 41 1 0 41 42 2 0 42 43 1 0 42 3 1 0 40 7 1 0 39 11 1 0 26 17 1 0 36 28 1 0 1 44 1 0 1 45 1 0 1 46 1 0 4 47 1 0 5 48 1 0 7 49 1 1 8 50 1 0 8 51 1 0 13 52 1 0 14 53 1 0 17 54 1 6 19 55 1 6 20 56 1 0 20 57 1 0 21 58 1 0 22 59 1 1 23 60 1 0 24 61 1 6 25 62 1 0 26 63 1 6 28 64 1 1 30 65 1 1 31 66 1 0 31 67 1 0 31 68 1 0 32 69 1 1 33 70 1 0 34 71 1 1 35 72 1 0 36 73 1 6 37 74 1 0 38 75 1 0 41 76 1 0 43 77 1 0 M END

Standard InCHIKey	ARGKVCXINMKCAZ-NRRCNVALSA-N
Standard InCHI	InChI=1S/C28H34O15/c1-10-21(33)23(35)25(37)27(39-10)43-26-24(36)22(34)19(9-29)42-28(26)40-12-6-14(31)20-15(32)8-17(41-18(20)7-12)11-3-4-16(38-2)13(30)5-11/h3-7,10,17,19,21-31,33-37H,8-9H2,1-2H3/t10-,17+,19-,21+,22-,23+,24+,25-,26-,27+,28-/m1/s1
SMILES	COC1=CC=C([C@@H]2CC(=O)C3=C(O)C=C(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O[C@@H]4O[C@H](C)[C@H](O)[C@H](O)[C@H]4O)C=C3O2)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	610.19	Volume:	563.46 ? Van der Waals volume.
Dense:	1.083	LogP:	0.274 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.135 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.185 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	30.0
TPSA:	234.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.185	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.812	Fsp³:	0.536
MCE-18:	120.977 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.615	Fluc inhibitor:	0.483 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.105 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.355 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.125	Promiscuous compounds:	0.393

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.596	MDCK Permeability:	-5.23
Pgp-inhibitor:	0.0	Pgp-substrate:	0.201
PAMPA:	0.992 ? 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):	0.969
20% Bioavailability (F20%):	0.284	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.15
Plasma Protein Binding (PPB):	78.591%	Volume Distribution (VD):	-0.298
Fu:	19.156% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.396
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.009	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.056
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.466
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.013
HLM stability:	0.715 ? 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):

1.426

Half-life (T1/2):

3.578

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.073
Human Hepatotoxicity (H-HT):	0.875	Drug-induced Liver Injury (DILI):	0.995
AMES Toxicity:	0.985	Rat Oral Acute Toxicity:	0.065
Maximum Recommended Daily Dose:	0.029	Skin Sensitization:	1.0
Carcinogencity:	0.184	Eye Corrosion:	0.0
Eye Irritation:	0.351	Respiratory Toxicity:	0.159
Drug-induced Neurotoxicity:	0.046	Ototoxicity:	0.982
Hematotoxicity:	0.622	Drug-induced Nephrotoxicity:	0.978
Genotoxicity:	0.967	RPMI-8226 Immunitoxicity:	0.449
A549 Cytotoxicity:	0.981	Hek293 Cytotoxicity:	0.675
BCF:	0.38 ? 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:	3.027 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.749 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.857 ? 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
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0031-9422(99)00119-3]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	fruit	n.a.	PMID[10606547]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10606602]
NPO20577	Citrus sudachi	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16933871]
NPO31471	Poncirus trifoliata	Species	Rutaceae	Eukaryota	n.a.	fruit	n.a.	PMID[17666859]
NPO7651	Citrus spp.	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22472691]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35143705]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35268681]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36378844]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38139796]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38308284]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38498554]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39410132]
NPO20577	Citrus sudachi	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7651	Citrus spp.	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31471	Poncirus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	Essential Oil	n.a.	n.a.	Database[FooDB]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	Flower	n.a.	n.a.	Database[FooDB]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	Leaf Essent. Oil	n.a.	n.a.	Database[FooDB]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO31471	Poncirus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	Fruits	n.a.		Database[Phenol-Explorer]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7651	Citrus spp.	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31471	Poncirus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7317	Citrus aurantium	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20577	Citrus sudachi	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO319	Citrus limon	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10082	Citrus unshiu	Species	Rutaceae	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 NPC542823 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	14943
0.1-0.2	28981
0.2-0.3	5281
0.3-0.4	569
0.4-0.5	55
0.5-0.6	13
0.6-0.7	6
0.7-0.8	0
0.8-0.85	6
0.85-0.9	1
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC105095
1.0	High Similarity	NPC177731
1.0	High Similarity	NPC725
0.8861	High Similarity	NPC97285
0.8415	Intermediate Similarity	NPC291124
0.8415	Intermediate Similarity	NPC131157
0.8171	Intermediate Similarity	NPC142860
0.8171	Intermediate Similarity	NPC152538
0.8171	Intermediate Similarity	NPC246469
0.8171	Intermediate Similarity	NPC89088
0.7711	Intermediate Similarity	NPC105283
0.6966	Remote Similarity	NPC44328
0.6966	Remote Similarity	NPC79056
0.6489	Remote Similarity	NPC261254
0.631	Remote Similarity	NPC219163
0.6162	Remote Similarity	NPC241196
0.6136	Remote Similarity	NPC236934
0.5977	Remote Similarity	NPC29830
0.5876	Remote Similarity	NPC47140
0.5833	Remote Similarity	NPC293629
0.5814	Remote Similarity	NPC97052
0.5789	Remote Similarity	NPC43587
0.5747	Remote Similarity	NPC39351
0.5714	Remote Similarity	NPC18727
0.5607	Remote Similarity	NPC469371
0.5604	Remote Similarity	NPC479540
0.5579	Remote Similarity	NPC271270
0.5556	Remote Similarity	NPC5778
0.5432	Remote Similarity	NPC607702
0.5055	Remote Similarity	NPC26195

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC542823 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4302
0.1-0.2	4716
0.2-0.3	125
0.3-0.4	5
0.4-0.5	1
0.5-0.6	0
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	Drug ID	Developmental Stage
0.6966	Remote Similarity	NPD7074	Phase 3

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