NPASS Compound

Natural Product: NPC588937

Natural Product ID	NPC588937
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-[[(2~{R},3~{S},4~{S},5~{S},6~{S})-6-(5,6-dihydroxy-4-oxo-2-phenyl-chromen-7-yl)oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methoxy]-3-oxo-propanoic acid
IUPAC Name	3-[[(2~{R},3~{S},4~{S},5~{S},6~{S})-6-(5,6-dihydroxy-4-oxo-2-phenyl-chromen-7-yl)oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methoxy]-3-oxo-propanoic acid
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 59 62 0 0 0 0 0 0 0 0999 V2000 -8.7774 -2.9336 0.5323 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6145 -2.6603 0.1218 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5786 -2.9492 0.9840 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3377 -2.0689 -1.1893 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8637 -1.8672 -1.3577 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1117 -2.2150 -0.4139 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3197 -1.3242 -2.4898 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9494 -1.1120 -2.6941 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3872 -0.1689 -1.6863 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0148 0.0529 -1.8863 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5662 0.7260 -0.7217 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2119 0.7398 -0.6051 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6871 0.3192 0.3163 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0652 0.5148 0.0791 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0393 0.1219 0.9545 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6325 -0.4932 2.1187 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2838 -0.6935 2.3681 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8994 -1.3167 3.5509 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2932 -0.2916 1.4736 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0260 -0.5478 1.8363 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6068 -0.8906 3.0038 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2733 -1.4468 4.0605 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9434 -0.6462 2.6670 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2948 -0.0281 1.4907 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6716 0.2505 1.0914 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9636 0.8747 -0.1104 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2520 1.1534 -0.5147 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3135 0.8061 0.2938 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0555 0.1851 1.4932 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7387 -0.0883 1.8837 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3098 0.3233 0.6949 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0471 2.1733 -0.8899 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9607 3.0018 -1.1700 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0959 2.2632 -1.9486 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5725 2.1558 -3.2365 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1276 1.1739 -1.7574 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8179 1.4295 -0.5886 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7172 -3.0636 1.9975 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8147 -1.0770 -1.3475 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7464 -2.7539 -1.9845 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7937 -0.7418 -3.7414 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4495 -2.0936 -2.5493 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5421 -0.5577 -0.6659 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1314 0.2717 0.1006 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3514 0.9945 -0.8328 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8307 -2.3415 3.5266 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4696 -1.4569 1.6397 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6962 -0.9549 3.3538 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1238 1.1494 -0.7500 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4666 1.6456 -1.4650 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3343 1.0254 -0.0228 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8935 -0.0820 2.1182 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5819 -0.5744 2.8286 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4941 2.4673 0.0787 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2551 2.4523 -1.5556 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5998 3.2432 -1.8709 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6040 2.2447 -3.2478 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8028 1.1671 -2.6481 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8011 1.4575 -0.7165 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 16 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 24 31 1 0 11 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 36 9 1 0 19 13 1 0 30 25 1 0 31 15 1 0 3 38 1 0 4 39 1 0 4 40 1 0 8 41 1 0 8 42 1 0 9 43 1 1 11 44 1 1 14 45 1 0 18 46 1 0 20 47 1 0 23 48 1 0 26 49 1 0 27 50 1 0 28 51 1 0 29 52 1 0 30 53 1 0 32 54 1 1 33 55 1 0 34 56 1 6 35 57 1 0 36 58 1 6 37 59 1 0 M END

Standard InCHIKey	NLRUTPIOMCJQKC-MEOHWMTASA-N
Standard InCHI	InChI=1S/C24H22O13/c25-11-6-12(10-4-2-1-3-5-10)35-13-7-14(19(29)21(31)18(11)13)36-24-23(33)22(32)20(30)15(37-24)9-34-17(28)8-16(26)27/h1-7,15,20,22-24,29-33H,8-9H2,(H,26,27)/t15-,20-,22+,23+,24-/m1/s1
SMILES	O=C(O)CC(=O)OC[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC=CC=C2)O3)[C@@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	518.11	Volume:	477.343 ? Van der Waals volume.
Dense:	1.085	LogP:	0.786 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.304 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.4 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	26.0
TPSA:	213.42 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.139	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.04	Fsp³:	0.292
MCE-18:	89.71 ? 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:	0.411	Fluc inhibitor:	0.255 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.834 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.765 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.057	Promiscuous compounds:	0.367

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.416	MDCK Permeability:	-5.221
Pgp-inhibitor:	0.0	Pgp-substrate:	0.026
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):	0.001
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.125
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.837
Plasma Protein Binding (PPB):	96.277%	Volume Distribution (VD):	-0.309
Fu:	3.777% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.134
BSEP inhibitor:	0.646

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.98
HLM stability:	0.004 ? 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):

1.707

Half-life (T1/2):

2.836

ADMET: Toxicity

hERG Blockers:	0.008	hERG Blockers (10um):	0.06
Human Hepatotoxicity (H-HT):	0.284	Drug-induced Liver Injury (DILI):	0.919
AMES Toxicity:	0.368	Rat Oral Acute Toxicity:	0.097
Maximum Recommended Daily Dose:	0.115	Skin Sensitization:	0.82
Carcinogencity:	0.132	Eye Corrosion:	0.0
Eye Irritation:	0.449	Respiratory Toxicity:	0.032
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.818
Hematotoxicity:	0.224	Drug-induced Nephrotoxicity:	0.598
Genotoxicity:	0.815	RPMI-8226 Immunitoxicity:	0.046
A549 Cytotoxicity:	0.006	Hek293 Cytotoxicity:	0.029
BCF:	0.22 ? 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:	2.815 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.102 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.462 ? 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
NPO44943	Cephalocereus senilis	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC588937 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	17491
0.1-0.2	29478
0.2-0.3	2130
0.3-0.4	573
0.4-0.5	153
0.5-0.6	26
0.6-0.7	4
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
0.7143	Intermediate Similarity	NPC46202
0.7143	Intermediate Similarity	NPC64051
0.6989	Remote Similarity	NPC229409
0.6905	Remote Similarity	NPC45618
0.6782	Remote Similarity	NPC237435
0.6067	Remote Similarity	NPC146792
0.5978	Remote Similarity	NPC43211
0.5957	Remote Similarity	NPC477848
0.5824	Remote Similarity	NPC58716
0.5806	Remote Similarity	NPC115760
0.5789	Remote Similarity	NPC172807
0.5789	Remote Similarity	NPC211594
0.5743	Remote Similarity	NPC479766
0.5567	Remote Similarity	NPC254540
0.5534	Remote Similarity	NPC479765
0.5429	Remote Similarity	NPC472994
0.5288	Remote Similarity	NPC270675
0.5288	Remote Similarity	NPC195685
0.5248	Remote Similarity	NPC22062
0.5248	Remote Similarity	NPC473634
0.5248	Remote Similarity	NPC138811
0.5234	Remote Similarity	NPC603856
0.5196	Remote Similarity	NPC204693
0.5185	Remote Similarity	NPC275722
0.5185	Remote Similarity	NPC599948
0.5149	Remote Similarity	NPC44931
0.5091	Remote Similarity	NPC472993
0.5048	Remote Similarity	NPC473623
0.5048	Remote Similarity	NPC483707
0.5048	Remote Similarity	NPC209296
0.5047	Remote Similarity	NPC298171
0.5046	Remote Similarity	NPC121703

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC588937 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3382
0.1-0.2	5638
0.2-0.3	120
0.3-0.4	4
0.4-0.5	4
0.5-0.6	1
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
0.6782	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.5048	Remote Similarity	NPD7054	Phase 4

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