NPASS Compound

Natural Product: NPC476620

Natural Product ID	NPC476620
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(1,3,6,7-tetrahydroxy-9-oxoxanthen-2-yl)oxyoxan-2-yl]methyl (E)-3-(4-hydroxyphenyl)prop-2-enoate
IUPAC Name	[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(1,3,6,7-tetrahydroxy-9-oxoxanthen-2-yl)oxyoxan-2-yl]methyl (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	45481963
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes [CHEMONTID:0000204] Xanthones

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 70 0 0 0 0 0 0 0 0999 V2000 -7.9155 1.8668 1.6263 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2321 2.3363 1.5826 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1995 1.6127 0.9225 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8420 0.4411 0.3206 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5481 -0.0167 0.3654 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5447 0.6973 1.0286 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1865 0.2012 1.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1879 0.8096 1.6734 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8391 0.2275 1.6596 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9220 0.8415 2.2482 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5543 -0.9485 1.0331 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2996 -1.5759 0.9675 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2927 -0.6859 0.2721 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8514 -0.1344 -0.9768 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4629 -0.8245 -2.2337 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4339 -1.9349 -1.9855 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5511 -1.3258 -1.0182 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0864 -1.3320 0.2175 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7436 -2.0377 -0.8872 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0181 -1.5306 -1.0099 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6837 -1.0001 0.1016 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9599 -0.4892 -0.0014 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6258 -0.4845 -1.2113 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9840 -1.0023 -2.3111 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6939 -1.5177 -2.2017 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1460 -2.0103 -3.3631 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8593 0.0091 -1.3096 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5049 0.5103 -0.2872 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7981 1.0181 -0.4329 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4819 1.5494 0.6509 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8821 1.5795 1.8911 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6164 1.0776 2.0121 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9067 0.5417 0.9562 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6320 0.0381 1.0861 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0821 0.0612 2.2063 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5995 2.1219 2.9618 O 0 0 0 0 0 0 0 0 0 0 0 0 10.7642 2.0519 0.5003 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0290 -0.9966 1.3263 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0931 -2.2482 -3.2134 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5364 -1.2608 -2.9861 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6146 1.2593 -1.0687 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.5344 2.0598 0.8616 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1643 2.4496 2.1505 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4788 3.2661 2.0709 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5695 -0.1596 -0.2093 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2279 -0.9500 -0.1055 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9376 -0.7463 0.5683 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3537 1.7253 2.1758 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9767 -1.7493 2.0368 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3879 -2.5414 0.4252 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1220 0.1887 0.9709 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9797 -0.2052 -0.9055 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9117 -0.0827 -2.8809 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0031 -2.7711 -1.5266 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7695 -0.2837 -1.3357 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5004 -1.0003 -3.2554 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3586 -1.5893 -4.2803 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2319 0.9781 -1.4156 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1546 1.1061 2.9881 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0371 1.4310 3.5861 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5165 1.4041 0.3532 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4307 -0.1824 1.4961 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1695 -3.1575 -3.5049 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2984 -1.9715 -3.6293 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7619 1.6884 -0.1910 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2280 1.5247 1.3760 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 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 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 23 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 31 36 1 0 30 37 1 0 21 38 1 0 16 39 1 0 15 40 1 0 14 41 1 0 3 42 1 0 6 1 1 0 18 13 1 0 25 20 1 0 34 22 1 0 33 28 1 0 1 43 1 0 2 44 1 0 4 45 1 0 5 46 1 0 7 47 1 0 8 48 1 0 12 49 1 0 12 50 1 0 13 51 1 1 14 52 1 1 15 53 1 6 16 54 1 1 17 55 1 6 24 56 1 0 26 57 1 0 29 58 1 0 32 59 1 0 36 60 1 0 37 61 1 0 38 62 1 0 39 63 1 0 40 64 1 0 41 65 1 0 42 66 1 0 M END

Standard InCHIKey	LKAUZCQGGQBXJB-KSSKDEGSSA-N
Standard InCHI	InChI=1S/C28H24O14/c29-12-4-1-11(2-5-12)3-6-20(33)39-10-19-23(35)25(37)26(38)28(41-19)42-27-16(32)9-18-21(24(27)36)22(34)13-7-14(30)15(31)8-17(13)40-18/h1-9,19,23,25-26,28-32,35-38H,10H2/b6-3+/t19-,23-,25+,26-,28+/m1/s1
SMILES	C1=CC(=CC=C1/C=C/C(=O)OC[C@@H]2[C@H]([C@@H]([C@H]([C@@H](O2)OC3=C(C4=C(C=C3O)OC5=CC(=C(C=C5C4=O)O)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	584.12	Volume:	541.487 ? Van der Waals volume.
Dense:	1.079	LogP:	1.187 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.164 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.178 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	31.0
TPSA:	236.81 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	14.0

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:	4.289	Fsp³:	0.214
MCE-18:	108.706 ? 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:	1
Colloidal aggregators:	0.757	Fluc inhibitor:	0.579 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.958 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.986 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.139	Promiscuous compounds:	0.81

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.485	MDCK Permeability:	-5.041
Pgp-inhibitor:	0.001	Pgp-substrate:	0.359
PAMPA:	0.987 ? 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):	0.012
20% Bioavailability (F20%):	0.969	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.018
Plasma Protein Binding (PPB):	85.385%	Volume Distribution (VD):	-0.046
Fu:	12.198% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.983
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.494
BSEP inhibitor:	0.824

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.12
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.399
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.971
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.46 ? 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):

3.241

Half-life (T1/2):

3.02

ADMET: Toxicity

hERG Blockers:	0.047	hERG Blockers (10um):	0.581
Human Hepatotoxicity (H-HT):	0.442	Drug-induced Liver Injury (DILI):	0.979
AMES Toxicity:	0.856	Rat Oral Acute Toxicity:	0.133
Maximum Recommended Daily Dose:	0.776	Skin Sensitization:	0.998
Carcinogencity:	0.208	Eye Corrosion:	0.0
Eye Irritation:	0.922	Respiratory Toxicity:	0.058
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.623
Hematotoxicity:	0.012	Drug-induced Nephrotoxicity:	0.115
Genotoxicity:	0.985	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.862	Hek293 Cytotoxicity:	0.745
BCF:	0.688 ? 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:	3.553 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.703 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.319 ? 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
NPO33596	Arrabidaea patellifera	Species	Bignoniaceae	Eukaryota	leaves	Valle de Antn, los Llanitos, Panama	2003-APR	PMID[18950229]

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	1
Ratio	1
EC50	1

Activity Type	# Activity
Organism	1
Others	2

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
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	>	38200	nM	PMID[18950229]
NPT1	Others	Radical scavenging activity	n.a.	Ratio	=	0.23	n.a.	PMID[18950229]
NPT2	Others	Unspecified	n.a.	EC50	=	1480	nM	PMID[18950229]

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 NPC476620 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	14751
0.1-0.2	30307
0.2-0.3	3833
0.3-0.4	789
0.4-0.5	140
0.5-0.6	31
0.6-0.7	3
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
0.6737	Remote Similarity	NPC476619
0.6465	Remote Similarity	NPC36138
0.6061	Remote Similarity	NPC476622
0.596	Remote Similarity	NPC476621
0.5922	Remote Similarity	NPC223426
0.5909	Remote Similarity	NPC291153
0.5905	Remote Similarity	NPC470416
0.5882	Remote Similarity	NPC80068
0.5882	Remote Similarity	NPC85751
0.5882	Remote Similarity	NPC19240
0.5882	Remote Similarity	NPC477629
0.5784	Remote Similarity	NPC270675
0.5784	Remote Similarity	NPC195685
0.5714	Remote Similarity	NPC476618
0.5699	Remote Similarity	NPC10205
0.566	Remote Similarity	NPC599948
0.5579	Remote Similarity	NPC204937
0.5566	Remote Similarity	NPC214621
0.5566	Remote Similarity	NPC34267
0.5556	Remote Similarity	NPC477895
0.5505	Remote Similarity	NPC217520
0.5472	Remote Similarity	NPC472994
0.5421	Remote Similarity	NPC81042
0.5421	Remote Similarity	NPC603856
0.5326	Remote Similarity	NPC34287
0.5326	Remote Similarity	NPC157898
0.5273	Remote Similarity	NPC480796
0.5273	Remote Similarity	NPC472993
0.5253	Remote Similarity	NPC476870
0.5204	Remote Similarity	NPC476869
0.5204	Remote Similarity	NPC476866
0.5133	Remote Similarity	NPC139571
0.5096	Remote Similarity	NPC271848
0.5052	Remote Similarity	NPC291296

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476620 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3889
0.1-0.2	5198
0.2-0.3	53
0.3-0.4	10
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