NPASS Compound

Natural Product: NPC319628

Natural Product ID	NPC319628
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1,4-Bis[[(E)-3-(3,4-Dihydroxyphenyl)Prop-2-Enoyl]Oxy]-3,5-Dihydroxycyclohexane-1-Carboxylic Acid
IUPAC Name	1,4-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-3,5-dihydroxycyclohexane-1-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1966984
PubChem CID	5316647
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000129] Alcohols and polyols [CHEMONTID:0001292] Cyclic alcohols and derivatives [CHEMONTID:0002509] Cyclitols and derivatives [CHEMONTID:0002512] Quinic acids and 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 61 63 0 0 0 0 0 0 0 0999 V2000 0.1615 1.0311 -1.0774 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0736 0.9119 -1.9247 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6205 -0.4816 -2.0533 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9260 -1.3650 -1.0386 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5374 -1.3960 -1.3446 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1646 -0.0205 -1.4171 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6677 0.1999 -2.7858 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9110 0.1578 -3.7736 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9992 0.4608 -3.0129 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3095 0.0535 -0.5739 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2803 -0.0891 0.7923 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1596 -0.3029 1.3361 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5043 0.0020 1.6046 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6367 0.2220 1.0109 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8785 0.3251 1.7299 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0514 0.5624 1.0001 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2563 0.6681 1.6468 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2893 0.5371 3.0184 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1362 0.3042 3.7322 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9130 0.1948 3.0971 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5061 0.6427 3.6838 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4230 0.9058 0.9031 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4004 -2.6754 -1.1251 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0019 -0.5411 -1.7641 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9161 -1.0710 -2.6272 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3753 -1.5153 -3.7473 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3211 -1.2361 -2.5540 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2992 -1.0111 -1.7816 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4489 -0.4219 -0.4899 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4442 0.1527 0.2592 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6636 0.6959 1.5288 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9288 0.6616 2.0616 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9577 0.0939 1.3378 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7381 -0.4308 0.1085 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1532 1.1969 3.3164 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6288 1.2589 2.2396 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0880 1.7757 -1.4355 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1216 1.0650 0.0018 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6224 2.0441 -1.2837 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8418 1.3246 -2.9283 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4715 -0.9274 -3.0543 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1009 -0.9298 -0.0394 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0111 -2.0135 -0.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7756 -1.9306 -2.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3434 0.6586 -3.9440 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4147 -0.1165 2.6515 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6578 0.3346 -0.0734 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0001 0.6618 -0.0784 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1780 0.2035 4.8099 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0416 0.0108 3.7189 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0786 1.4572 3.5462 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8191 1.8446 1.0185 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8165 -3.2477 -1.6739 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7230 -1.7595 -3.5431 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3047 -1.3546 -2.2183 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4564 0.2159 -0.1041 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9362 0.1001 1.8197 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5466 -0.8581 -0.4182 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0025 1.6893 3.5007 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5424 1.2613 3.2398 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8783 1.6490 -2.0134 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 6 7 1 0 7 8 2 0 7 9 1 0 6 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 2 3 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 18 21 1 0 17 22 1 0 4 23 1 0 3 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 2 3 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 32 35 1 0 31 36 1 0 2 37 1 0 6 1 1 0 20 15 1 0 34 29 1 0 1 38 1 0 1 39 1 0 2 40 1 0 3 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 9 45 1 0 13 46 1 0 14 47 1 0 16 48 1 0 19 49 1 0 20 50 1 0 21 51 1 0 22 52 1 0 23 53 1 0 27 54 1 0 28 55 1 0 30 56 1 0 33 57 1 0 34 58 1 0 35 59 1 0 36 60 1 0 37 61 1 0 M END

Standard InCHIKey	IYXQRCXQQWUFQV-FCXRPNKRSA-N
Standard InCHI	InChI=1S/C25H24O12/c26-15-5-1-13(9-17(15)28)3-7-21(32)36-23-19(30)11-25(24(34)35,12-20(23)31)37-22(33)8-4-14-2-6-16(27)18(29)10-14/h1-10,19-20,23,26-31H,11-12H2,(H,34,35)/b7-3+,8-4+
SMILES	C1C(C(C(CC1(C(=O)O)OC(=O)C=CC2=CC(=C(C=C2)O)O)O)OC(=O)C=CC3=CC(=C(C=C3)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.13	Volume:	491.768 ? Van der Waals volume.
Dense:	1.05	LogP:	1.723 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.575 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.337 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	23.0
TPSA:	211.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.156	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.878	Fsp³:	0.24
MCE-18:	81.29 ? 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:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.774	Fluc inhibitor:	0.92 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.361 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.669 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.546	Promiscuous compounds:	0.568

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.687	MDCK Permeability:	-4.984
Pgp-inhibitor:	0.0	Pgp-substrate:	0.002
PAMPA:	1.0 ? 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):	0.74
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.873
Plasma Protein Binding (PPB):	57.451%	Volume Distribution (VD):	-0.026
Fu:	42.493% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.01	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.029
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.971
HLM stability:	0.0 ? 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):

4.884

Half-life (T1/2):

2.804

ADMET: Toxicity

hERG Blockers:	0.071	hERG Blockers (10um):	0.449
Human Hepatotoxicity (H-HT):	0.298	Drug-induced Liver Injury (DILI):	0.295
AMES Toxicity:	0.344	Rat Oral Acute Toxicity:	0.19
Maximum Recommended Daily Dose:	0.863	Skin Sensitization:	0.995
Carcinogencity:	0.035	Eye Corrosion:	0.0
Eye Irritation:	0.107	Respiratory Toxicity:	0.056
Drug-induced Neurotoxicity:	0.028	Ototoxicity:	0.966
Hematotoxicity:	0.002	Drug-induced Nephrotoxicity:	0.306
Genotoxicity:	0.373	RPMI-8226 Immunitoxicity:	0.014
A549 Cytotoxicity:	0.619	Hek293 Cytotoxicity:	0.429
BCF:	0.564 ? 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:	3.17 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.577 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.186 ? 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
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/S0031-9422(00)94055-X]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	flower	n.a.	DOI[10.3390/70200245]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24617303]
NPO17612	Xanthium sibiricum	Species	Asteraceae	Eukaryota	Fruits	n.a.	n.a.	PMID[26110443]
NPO17612	Xanthium sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17612	Xanthium sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17612	Xanthium sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO17612	Xanthium sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17612	Xanthium sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17612	Xanthium sibiricum	Species	Asteraceae	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
Potency	24
IC50	8
AC50	1

Activity Type	# Activity
Individual protein	24
Cell line	1
Organism	2
Others	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2741	Individual protein	Pyruvate kinase	Leishmania mexicana	Potency	=	1995.3	nM	PubChem BioAssay data set
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	11220.2	nM	PubChem BioAssay data set
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	Potency	n.a.	12589.3	nM	PubChem BioAssay data set
NPT100	Individual protein	Glutaminase kidney isoform, mitochondrial	Homo sapiens	Potency	n.a.	6309.6	nM	PubChem BioAssay data set
NPT1853	Individual protein	Putative uncharacterized protein	Trypanosoma brucei brucei (strain 927/4 GUTat10.1)	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT1040	Individual protein	Human immunodeficiency virus type 1 Tat protein	Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)	IC50	n.a.	85194.0	nM	PubChem BioAssay data set
NPT9	Individual protein	DNA polymerase eta	Homo sapiens	Potency	n.a.	19952.6	nM	PubChem BioAssay data set
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	3162.3	nM	PubChem BioAssay data set
NPT4413	Individual protein	M18 aspartyl aminopeptidase	Plasmodium falciparum 3D7	IC50	=	1945.0	nM	PubChem BioAssay data set
NPT60	Individual protein	Lysosomal alpha-glucosidase	Homo sapiens	Potency	=	1764.7	nM	PubChem BioAssay data set
NPT59	Individual protein	DNA polymerase beta	Homo sapiens	Potency	=	1412.5	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	5011.9	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	23778.1	nM	PubChem BioAssay data set
NPT52	Individual protein	Pyruvate kinase isozymes M1/M2	Homo sapiens	Potency	=	4466.8	nM	PubChem BioAssay data set
NPT53	Individual protein	4'-phosphopantetheinyl transferase ffp	Bacillus subtilis	Potency	=	44668.4	nM	PubChem BioAssay data set
NPT864	Individual protein	Lethal(3)malignant brain tumor-like protein 1	Homo sapiens	Potency	=	1000.0	nM	PubChem BioAssay data set
NPT469	Individual protein	Cathepsin L	Homo sapiens	IC50	>	59642.0	nM	PubChem BioAssay data set
NPT532	Individual protein	Lysine-specific demethylase 4A	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT5	Individual protein	Histone-lysine N-methyltransferase, H3 lysine-9 specific 3	Homo sapiens	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT864	Individual protein	Lethal(3)malignant brain tumor-like protein 1	Homo sapiens	Potency	n.a.	75.2	nM	PubChem BioAssay data set
NPT4675	Individual protein	Histone-lysine N-methyltransferase NSD2	Homo sapiens	AC50	=	5430.0	nM	PubChem BioAssay data set
NPT49	Individual protein	DNA-(apurinic or apyrimidinic site) lyase	Homo sapiens	Potency	n.a.	12589.3	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT71	Cell line	HEK293	Homo sapiens	Potency	n.a.	7943.3	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	1651.1	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	657.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	=	18356.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	31880.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	>	67562.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	3759.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	2073.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	n.a.	16230.0	nM	PubChem BioAssay data set

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 NPC319628 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	8629
0.1-0.2	37386
0.2-0.3	3335
0.3-0.4	370
0.4-0.5	87
0.5-0.6	40
0.6-0.7	5
0.7-0.8	1
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
0.7143	Intermediate Similarity	NPC284948
0.7143	Intermediate Similarity	NPC303090
0.7143	Intermediate Similarity	NPC301382
0.7143	Intermediate Similarity	NPC37331
0.7119	Intermediate Similarity	NPC219428
0.6727	Remote Similarity	NPC474275
0.6716	Remote Similarity	NPC220664
0.6462	Remote Similarity	NPC477334
0.6081	Remote Similarity	NPC192568
0.6032	Remote Similarity	NPC13818
0.597	Remote Similarity	NPC283560
0.597	Remote Similarity	NPC24295
0.5968	Remote Similarity	NPC26241
0.5862	Remote Similarity	NPC224208
0.5862	Remote Similarity	NPC41661
0.5821	Remote Similarity	NPC206095
0.5821	Remote Similarity	NPC35702
0.5821	Remote Similarity	NPC224389
0.5789	Remote Similarity	NPC233669
0.5738	Remote Similarity	NPC488563
0.5692	Remote Similarity	NPC474875
0.569	Remote Similarity	NPC281277
0.5672	Remote Similarity	NPC471027
0.5672	Remote Similarity	NPC37250
0.5672	Remote Similarity	NPC142703
0.5672	Remote Similarity	NPC152942
0.5672	Remote Similarity	NPC9991
0.5672	Remote Similarity	NPC302857
0.5672	Remote Similarity	NPC600892
0.5658	Remote Similarity	NPC471076
0.5593	Remote Similarity	NPC309434
0.5517	Remote Similarity	NPC217052
0.5517	Remote Similarity	NPC329344
0.5517	Remote Similarity	NPC237506
0.5517	Remote Similarity	NPC32626
0.5493	Remote Similarity	NPC477335
0.5479	Remote Similarity	NPC297517
0.5441	Remote Similarity	NPC477333
0.5405	Remote Similarity	NPC42464
0.5333	Remote Similarity	NPC147192
0.5238	Remote Similarity	NPC251407
0.5238	Remote Similarity	NPC474895
0.5238	Remote Similarity	NPC168653
0.5176	Remote Similarity	NPC470896
0.5079	Remote Similarity	NPC132921
0.5077	Remote Similarity	NPC258469
0.5077	Remote Similarity	NPC43158
0.5077	Remote Similarity	NPC610147
0.5067	Remote Similarity	NPC156875
0.506	Remote Similarity	NPC473275

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC319628 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2710
0.1-0.2	6235
0.2-0.3	199
0.3-0.4	5
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7143	Intermediate Similarity	NPD6190	Approved

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