NPASS Compound

Natural Product: NPC253730

Natural Product ID	NPC253730
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Chalcomoracin
IUPAC Name	[(1R,2S,6S)-2-[2,6-dihydroxy-4-(6-hydroxy-1-benzofuran-2-yl)phenyl]-6-(2,4-dihydroxyphenyl)-4-methylcyclohex-3-en-1-yl]-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]methanone
Synonyms	Chalcomoracin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1808155
PubChem CID	14334313
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 84 89 0 0 0 0 0 0 0 0999 V2000 -6.8656 -3.0620 1.1137 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5137 -3.1045 0.4533 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4104 -3.0898 1.1806 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0882 -3.1303 0.5258 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2734 -1.9318 0.8738 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7158 -1.8847 2.1371 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8958 -2.9126 3.0587 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9720 -0.7874 2.4642 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7954 0.2380 1.5385 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3414 0.2011 0.2870 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0908 -0.9117 -0.0337 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6832 -1.0231 -1.2978 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1985 1.2636 -0.6631 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8459 1.1256 -1.7731 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3856 2.4993 -0.4857 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0622 2.3765 -0.7286 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4165 2.7376 -2.1455 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6412 3.3889 -2.9715 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6925 3.8589 -2.6194 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0179 3.6638 -1.1885 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8632 4.8876 -0.4064 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2976 5.6282 -0.3711 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4087 6.7815 0.3474 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6620 7.2496 1.0750 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8371 6.5321 1.0595 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9529 5.3687 0.3360 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1601 4.6692 0.3454 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5319 8.4187 1.7964 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1638 3.6609 -4.3719 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7114 1.0898 -0.4220 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6729 0.0924 -1.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0007 0.3029 -2.5973 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2974 -1.1020 -1.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9752 -1.3739 0.0727 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0038 -0.3657 1.0121 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3829 0.8395 0.7640 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4325 1.8450 1.7444 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6295 -2.6603 0.2953 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6822 -3.6295 -0.5853 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3344 -4.6541 -0.0925 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7433 -4.3694 1.1800 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2833 -3.0743 1.4267 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4419 -5.3276 1.8555 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7175 -6.5466 1.2481 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3094 -6.8423 -0.0361 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5980 -5.8601 -0.7166 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5816 -8.0563 -0.6487 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4597 -3.1698 -1.0452 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5381 -2.3582 0.5927 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7405 -2.8661 2.1826 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3011 -4.0756 1.0078 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4697 -3.0496 2.2545 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5398 -4.0549 0.8401 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2188 -3.1783 -0.5557 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1643 -3.6053 3.2341 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5114 -0.7127 3.4569 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2109 1.0660 1.8775 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0890 -1.4247 -2.0306 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5030 2.7351 0.6220 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5841 3.1674 -0.0996 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3927 2.4247 -2.4865 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8539 4.9428 -2.8559 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4084 3.3423 -3.3098 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1599 3.4494 -1.1679 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1472 5.3056 -0.9325 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3652 7.3110 0.3222 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7012 6.8886 1.6332 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5681 4.2902 1.1929 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2923 8.9976 1.7250 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2415 3.4727 -4.4196 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9139 4.7205 -4.5935 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6152 3.0451 -5.0922 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3888 -0.2104 -3.3785 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2435 -1.8647 -1.8879 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5166 -0.5264 1.9452 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1508 1.6571 2.6971 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4379 -2.5481 2.3434 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7681 -5.1240 2.8508 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2708 -7.3323 1.7564 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2653 -6.0478 -1.7121 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3404 -8.0954 -1.3260 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1116 -2.2254 -1.4923 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5019 -3.3074 -1.4151 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8777 -4.0584 -1.3891 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 10 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 24 28 1 0 18 29 1 0 16 30 1 0 30 31 2 0 31 32 1 0 31 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 34 38 1 0 38 39 1 0 39 40 1 0 40 41 2 0 41 42 1 0 41 43 1 0 43 44 2 0 44 45 1 0 45 46 2 0 45 47 1 0 2 48 1 0 11 5 1 0 20 15 1 0 26 21 1 0 36 30 1 0 42 38 2 0 46 40 1 0 1 49 1 0 1 50 1 0 1 51 1 0 3 52 1 0 4 53 1 0 4 54 1 0 7 55 1 0 8 56 1 0 9 57 1 0 12 58 1 0 15 59 1 1 16 60 1 1 17 61 1 0 19 62 1 0 19 63 1 0 20 64 1 6 22 65 1 0 23 66 1 0 25 67 1 0 27 68 1 0 28 69 1 0 29 70 1 0 29 71 1 0 29 72 1 0 32 73 1 0 33 74 1 0 35 75 1 0 37 76 1 0 42 77 1 0 43 78 1 0 44 79 1 0 46 80 1 0 47 81 1 0 48 82 1 0 48 83 1 0 48 84 1 0 M END

Standard InCHIKey	SEHVRKPXIDOTRX-QQDDVHTNSA-N
Standard InCHI	InChI=1S/C39H36O9/c1-19(2)4-8-26-30(42)11-10-27(38(26)46)39(47)36-28(25-9-7-23(40)17-31(25)43)12-20(3)13-29(36)37-32(44)14-22(15-33(37)45)34-16-21-5-6-24(41)18-35(21)48-34/h4-7,9-11,13-18,28-29,36,40-46H,8,12H2,1-3H3/t28-,29+,36-/m1/s1
SMILES	CC(=CCc1c(O)ccc(c1O)C(=O)[C@H]1[C@H](C=C(C[C@@H]1c1ccc(cc1O)O)C)c1c(O)cc(cc1O)c1oc2c(c1)ccc(c2)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	648.24	Volume:	668.69 ? Van der Waals volume.
Dense:	0.969	LogP:	5.425 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.052 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.745 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	36.0
TPSA:	171.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	7.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.068	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.43	Fsp³:	0.205
MCE-18:	123.638 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.624 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.878 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.935 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.312	Promiscuous compounds:	0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.485	MDCK Permeability:	-4.84
Pgp-inhibitor:	0.004	Pgp-substrate:	0.06
PAMPA:	0.566 ? 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%):	0.977	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.986
Plasma Protein Binding (PPB):	93.915%	Volume Distribution (VD):	0.263
Fu:	7.376% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.789
BSEP inhibitor:	0.589

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.983	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.986	CYP2C9-substrate:	0.012
CYP2D6-inhibitor:	0.948	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.124	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):

0.483

Half-life (T1/2):

3.283

ADMET: Toxicity

hERG Blockers:	0.039	hERG Blockers (10um):	0.744
Human Hepatotoxicity (H-HT):	0.934	Drug-induced Liver Injury (DILI):	0.733
AMES Toxicity:	0.463	Rat Oral Acute Toxicity:	0.857
Maximum Recommended Daily Dose:	0.996	Skin Sensitization:	0.983
Carcinogencity:	0.013	Eye Corrosion:	0.0
Eye Irritation:	0.579	Respiratory Toxicity:	0.996
Drug-induced Neurotoxicity:	0.008	Ototoxicity:	0.501
Hematotoxicity:	0.042	Drug-induced Nephrotoxicity:	0.641
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.136
A549 Cytotoxicity:	0.901	Hek293 Cytotoxicity:	0.997
BCF:	1.516 ? 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:	5.01 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.359 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.858 ? 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
NPO28803	Artocarpus chama	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[15165133]
NPO27320	Morus notabilis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21737271]
NPO27089	Nectandra glabrescens	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27320	Morus notabilis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28584	Euphorbia indica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27589	Artemisia lehmanniana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29149	Zexmenia phyllocephala	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27280	Stachys spectabilis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27478	Geodia japonica	Species	Geodiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27071	Spirastrella coccinea	Species	Spirastrellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27147	Habenaria repens	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27368	Sinularia mayi	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28803	Artocarpus chama	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27478	Geodia japonica	Species	Geodiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29149	Zexmenia phyllocephala	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27147	Habenaria repens	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27280	Stachys spectabilis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27589	Artemisia lehmanniana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27368	Sinularia mayi	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28803	Artocarpus chama	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28584	Euphorbia indica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27089	Nectandra glabrescens	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27071	Spirastrella coccinea	Species	Spirastrellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27320	Morus notabilis	Species	Moraceae	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	7
Activity	2
MIC	1

Activity Type	# Activity
Individual protein	3
Cell line	2
Single protein	4
Organism	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	IC50	=	1940.0	nM	PMID[29275228]
NPT22768	Single protein	Phosphotyrosine protein phosphatase	Mycobacterium tuberculosis	IC50	=	1445.44	nM	PMID[29275228]
NPT22768	Single protein	Phosphotyrosine protein phosphatase	Mycobacterium tuberculosis	IC50	=	1430.0	nM	PMID[29275228]
NPT24759	Single protein	Protein-tyrosine phosphatase G1	Homo sapiens	IC50	=	8520.0	nM	PMID[29275228]
NPT3985	Individual protein	Probable low molecular weight protein-tyrosine-phosphatase	Mycobacterium tuberculosis	IC50	=	2430.0	nM	PMID[29275228]
NPT30142	Single protein	Enoyl-[acyl-carrier-protein] reductase (FabI)	Staphylococcus aureus	IC50	=	5500.0	nM	PMID[32883635]
NPT3997	Individual protein	Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP	Homo sapiens	IC50	=	7290.0	nM	PMID[29275228]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	109.99	%	PMID[21737271]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	125.36	%	PMID[21737271]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	4.0	ug.mL-1	PMID[32883635]

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 NPC253730 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	16649
0.1-0.2	30827
0.2-0.3	2241
0.3-0.4	109
0.4-0.5	19
0.5-0.6	8
0.6-0.7	1
0.7-0.8	0
0.8-0.85	2
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	NPC286230
0.8333	Intermediate Similarity	NPC169471
0.8333	Intermediate Similarity	NPC177836
0.617	Remote Similarity	NPC611245
0.5727	Remote Similarity	NPC101991
0.5701	Remote Similarity	NPC56049
0.5476	Remote Similarity	NPC167576
0.52	Remote Similarity	NPC110882
0.5149	Remote Similarity	NPC271944
0.5138	Remote Similarity	NPC59491
0.5138	Remote Similarity	NPC24748
0.5045	Remote Similarity	NPC477529

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC253730 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3493
0.1-0.2	5603
0.2-0.3	53
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