NPASS Compound

Natural Product: NPC548076

Natural Product ID	NPC548076
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NSC 339192
IUPAC Name	[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-chroman-7-yl]oxy-tetrahydropyran-2-yl]methyl (~{E})-3-(4-hydroxyphenyl)prop-2-enoate
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 70 74 0 0 0 0 0 0 0 0999 V2000 4.4450 1.5493 -1.6755 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7938 0.4003 -1.3939 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2138 0.0719 -1.1458 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1293 1.0134 -1.2238 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5516 0.7983 -0.9988 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4284 1.8764 -1.1085 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7831 1.7187 -0.9043 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3090 0.4772 -0.5831 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6724 0.3267 -0.3793 O 0 0 0 0 0 0 0 0 0 0 0 0 10.4754 -0.5900 -0.4701 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1112 -0.4096 -0.6802 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8685 -0.6127 -1.3022 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4953 -0.4150 -1.5156 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8617 0.5620 -0.5563 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5119 0.6772 -0.8547 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3004 0.7694 0.2751 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6558 -0.4719 0.7922 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9240 -0.9971 0.8833 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0978 -2.2769 1.4396 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3190 -2.8815 1.5718 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4585 -4.1524 2.1280 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4465 -2.2477 1.1571 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7873 -2.8387 1.2696 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8962 -4.0687 1.5157 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9576 -1.9389 1.0838 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6492 -1.0722 -0.1123 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7530 -0.1362 -0.4267 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0243 0.9878 0.3049 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0729 1.8138 -0.0505 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8598 1.5157 -1.1478 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9237 2.3539 -1.5081 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.6014 0.3850 -1.8990 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5463 -0.4110 -1.5097 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4772 -0.3341 0.1775 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3142 -0.9917 0.6069 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0729 -0.3644 0.4667 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3261 1.6759 1.3252 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4448 2.9426 0.7565 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6628 1.1976 1.7863 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6270 0.7366 3.0908 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1169 0.0867 0.8523 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4899 -0.1237 0.9826 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5001 -0.9385 -0.9008 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7456 2.0151 -1.4790 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0604 2.8620 -1.3573 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4591 2.5579 -0.9904 H 0 0 0 0 0 0 0 0 0 0 0 0 13.1125 -0.5647 -0.5115 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8141 -1.6022 -0.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4507 -1.2662 -0.5884 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2661 -0.0826 -2.5513 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9801 -1.4024 -1.3935 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3553 1.5433 -0.6971 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2077 1.3002 -0.0602 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2078 -2.7810 1.7686 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8112 -4.3003 3.0537 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9483 -1.2465 1.9749 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8954 -2.4897 0.9937 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4366 -1.7425 -0.9697 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4077 1.2176 1.1611 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3193 2.7097 0.5011 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8903 2.0217 -1.4114 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2303 0.1733 -2.7521 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3468 -1.2967 -2.1015 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0409 0.6130 0.0302 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4202 1.7592 2.1414 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0881 3.6224 1.2155 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4238 2.0205 1.6653 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5619 0.6243 3.4333 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6292 -0.8739 1.0598 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7115 -1.0549 1.2360 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 8 10 1 0 10 11 2 0 2 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 18 19 2 0 19 20 1 0 20 21 1 0 20 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 30 32 1 0 32 33 2 0 26 34 1 0 34 35 1 0 35 36 2 0 16 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 39 41 1 0 41 42 1 0 11 5 1 0 41 14 1 0 36 18 1 0 35 22 1 0 33 27 1 0 3 43 1 0 4 44 1 0 6 45 1 0 7 46 1 0 9 47 1 0 10 48 1 0 11 49 1 0 13 50 1 0 13 51 1 0 14 52 1 1 16 53 1 6 19 54 1 0 21 55 1 0 25 56 1 0 25 57 1 0 26 58 1 0 28 59 1 0 29 60 1 0 31 61 1 0 32 62 1 0 33 63 1 0 36 64 1 0 37 65 1 1 38 66 1 0 39 67 1 1 40 68 1 0 41 69 1 1 42 70 1 0 M END

Standard InCHIKey	PLORCKNHUZJPKH-PTROEBSBSA-N
Standard InCHI	InChI=1S/C30H28O12/c31-17-6-1-15(2-7-17)3-10-25(35)39-14-24-27(36)28(37)29(38)30(42-24)40-19-11-20(33)26-21(34)13-22(41-23(26)12-19)16-4-8-18(32)9-5-16/h1-12,22,24,27-33,36-38H,13-14H2/b10-3+/t22?,24-,27-,28+,29-,30-/m1/s1
SMILES	O=C(/C=C/C1=CC=C(O)C=C1)OC[C@H]1O[C@@H](OC2=CC(O)=C3C(=O)CC(C4=CC=C(O)C=C4)OC3=C2)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	580.16	Volume:	558.499 ? Van der Waals volume.
Dense:	1.039	LogP:	1.676 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.829 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.152 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	32.0
TPSA:	192.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.176	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.25	Fsp³:	0.267
MCE-18:	104.421 ? 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:	0.824	Fluc inhibitor:	0.792 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.342 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.805 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.215	Promiscuous compounds:	0.169

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.368	MDCK Permeability:	-5.114
Pgp-inhibitor:	0.418	Pgp-substrate:	0.034
PAMPA:	0.968 ? 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):	0.019
20% Bioavailability (F20%):	0.139	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.012
Plasma Protein Binding (PPB):	90.961%	Volume Distribution (VD):	-0.096
Fu:	8.755% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.917
BSEP inhibitor:	0.979

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.913
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.983
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.479
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.592 ? 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):

2.286

Half-life (T1/2):

3.057

ADMET: Toxicity

hERG Blockers:	0.154	hERG Blockers (10um):	0.55
Human Hepatotoxicity (H-HT):	0.722	Drug-induced Liver Injury (DILI):	0.948
AMES Toxicity:	0.878	Rat Oral Acute Toxicity:	0.118
Maximum Recommended Daily Dose:	0.549	Skin Sensitization:	0.984
Carcinogencity:	0.146	Eye Corrosion:	0.0
Eye Irritation:	0.397	Respiratory Toxicity:	0.038
Drug-induced Neurotoxicity:	0.122	Ototoxicity:	0.763
Hematotoxicity:	0.056	Drug-induced Nephrotoxicity:	0.919
Genotoxicity:	0.952	RPMI-8226 Immunitoxicity:	0.232
A549 Cytotoxicity:	0.773	Hek293 Cytotoxicity:	0.928
BCF:	0.947 ? 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:	3.821 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.828 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.467 ? 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
NPO960	Phlomis aurea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO960	Phlomis aurea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO960	Phlomis aurea	Species	Lamiaceae	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 NPC548076 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	13318
0.1-0.2	30838
0.2-0.3	4509
0.3-0.4	1001
0.4-0.5	146
0.5-0.6	33
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC67134
0.7831	Intermediate Similarity	NPC472876
0.7294	Intermediate Similarity	NPC271270
0.679	Remote Similarity	NPC39351
0.6556	Remote Similarity	NPC43587
0.6463	Remote Similarity	NPC291153
0.6129	Remote Similarity	NPC44328
0.6129	Remote Similarity	NPC79056
0.6064	Remote Similarity	NPC293629
0.6047	Remote Similarity	NPC29830
0.5882	Remote Similarity	NPC97052
0.5843	Remote Similarity	NPC10205
0.5843	Remote Similarity	NPC236934
0.5814	Remote Similarity	NPC219163
0.5714	Remote Similarity	NPC204937
0.5632	Remote Similarity	NPC157898
0.5484	Remote Similarity	NPC476869
0.5484	Remote Similarity	NPC476866
0.5455	Remote Similarity	NPC47140
0.5417	Remote Similarity	NPC142860
0.5417	Remote Similarity	NPC152538
0.5417	Remote Similarity	NPC246469
0.5417	Remote Similarity	NPC89088
0.5333	Remote Similarity	NPC43638
0.5269	Remote Similarity	NPC476867
0.5243	Remote Similarity	NPC80068
0.5229	Remote Similarity	NPC469371
0.5222	Remote Similarity	NPC206378
0.5189	Remote Similarity	NPC321916
0.5172	Remote Similarity	NPC479473
0.5172	Remote Similarity	NPC275721
0.5172	Remote Similarity	NPC479468
0.5172	Remote Similarity	NPC479474
0.5146	Remote Similarity	NPC270675
0.5146	Remote Similarity	NPC195685
0.5128	Remote Similarity	NPC329203
0.5128	Remote Similarity	NPC222342
0.5111	Remote Similarity	NPC26195
0.5106	Remote Similarity	NPC471405
0.5096	Remote Similarity	NPC477629
0.5056	Remote Similarity	NPC169248
0.5056	Remote Similarity	NPC72649
0.5052	Remote Similarity	NPC105283

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC548076 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4388
0.1-0.2	4671
0.2-0.3	83
0.3-0.4	6
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
0.6129	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