NPASS Compound

Natural Product: NPC475539

Natural Product ID	NPC475539
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Gaertneroside
IUPAC Name	methyl (1R,4aS,7R,7aS)-4'-[hydroxy-(4-hydroxyphenyl)methyl]-5'-oxo-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyspiro[4a,7a-dihydro-1H-cyclopenta[c]pyran-7,2'-furan]-4-carboxylate
Synonyms	Gaertneroside
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL507679
PubChem CID	44559436
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0004081] Iridoid O-glycosides

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 67 71 0 0 0 0 0 0 0 0999 V2000 5.0945 -3.5951 -1.0172 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9022 -3.0677 -1.5117 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1473 -2.4949 -0.3417 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9298 -1.9323 -0.6971 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5426 -1.1116 0.3635 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4914 -0.2659 0.0320 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8333 1.0778 0.0847 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7895 1.7022 -1.1720 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2076 3.0375 -1.2216 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1259 3.7617 -0.1246 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6118 3.2494 1.1835 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1016 1.8572 1.1023 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3633 2.0406 0.9096 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6485 3.4233 1.3704 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5518 4.0762 1.5165 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1326 1.2067 1.7453 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0215 0.4916 0.9919 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8874 -0.3701 1.4131 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8163 0.8802 -0.3961 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8544 1.7762 -0.4320 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5928 0.3282 -1.5151 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5117 -1.1205 -1.6883 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6171 -1.9553 -1.0526 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6176 -3.3306 -1.2855 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5152 -3.9038 -2.1618 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4091 -3.0678 -2.7967 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4178 -1.6955 -2.5723 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4825 -5.2789 -2.3658 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9392 0.6866 -1.3562 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5576 5.1465 -0.1703 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0108 5.6781 -1.2358 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5095 5.9904 0.9356 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9485 7.3543 0.8394 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2519 -1.9579 1.5725 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6025 -3.4020 1.3762 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8931 -3.6202 0.6375 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9725 -3.8035 1.4968 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5783 -4.1241 0.7449 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8890 -1.4986 2.7232 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6846 -2.8961 -0.6380 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0723 -2.3221 -2.3183 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3097 -3.9476 -1.8838 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8175 -1.7310 0.1268 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4515 -0.4898 0.6044 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9212 1.0931 0.3969 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5817 3.4183 -2.1646 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4251 3.3303 1.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2740 1.3601 2.1019 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6696 3.8185 1.5567 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4602 5.1245 1.8480 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5393 2.2068 -1.3919 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2799 0.7859 -2.4961 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9274 -1.4901 -0.3737 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8991 -3.9534 -0.7670 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1191 -3.5152 -3.4887 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1489 -1.0945 -3.1055 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7000 -5.9650 -1.6720 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1333 1.0252 -0.4551 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5504 7.8581 1.7465 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5015 7.8185 -0.0464 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0539 7.4157 0.8710 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1450 -1.9228 1.7789 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7226 -3.8594 2.3872 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8051 -4.5565 0.0439 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7227 -4.1638 2.3731 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9200 -4.6613 -0.0156 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3058 -0.8549 3.1615 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 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 13 16 1 1 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 25 28 1 0 21 29 1 0 10 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 5 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 35 38 1 0 34 39 1 0 36 3 1 0 12 7 1 0 20 13 1 0 27 22 1 0 15 11 1 0 1 40 1 0 2 41 1 0 2 42 1 0 3 43 1 1 5 44 1 1 7 45 1 1 9 46 1 0 11 47 1 1 12 48 1 1 14 49 1 0 15 50 1 0 20 51 1 0 21 52 1 0 23 53 1 0 24 54 1 0 26 55 1 0 27 56 1 0 28 57 1 0 29 58 1 0 33 59 1 0 33 60 1 0 33 61 1 0 34 62 1 1 35 63 1 1 36 64 1 6 37 65 1 0 38 66 1 0 39 67 1 0 M END

Standard InCHIKey	HGHZVZYRYYMUTI-WGYUZEAXSA-N
Standard InCHI	InChI=1S/C26H28O13/c1-35-22(33)15-10-36-24(38-25-21(32)20(31)19(30)16(9-27)37-25)17-13(15)6-7-26(17)8-14(23(34)39-26)18(29)11-2-4-12(28)5-3-11/h2-8,10,13,16-21,24-25,27-32H,9H2,1H3/t13-,16-,17-,18?,19-,20+,21-,24-,25+,26-/m1/s1
SMILES	OC[C@H]1O[C@@H](O[C@H]2OC=C([C@@H]3[C@H]2[C@]2(C=C3)OC(=O)C(=C2)C(c2ccc(cc2)O)O)C(=O)OC)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	548.15	Volume:	508.651 ? Van der Waals volume.
Dense:	1.078	LogP:	0.169 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.835 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.499 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	29.0
TPSA:	201.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.181	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.606	Fsp³:	0.462
MCE-18:	147.632 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.55	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.076 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.024 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.444	Promiscuous compounds:	0.201

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.027	MDCK Permeability:	-5.334
Pgp-inhibitor:	0.0	Pgp-substrate:	0.103
PAMPA:	0.995 ? 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):	0.003
20% Bioavailability (F20%):	0.253	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.764
Plasma Protein Binding (PPB):	73.916%	Volume Distribution (VD):	-0.339
Fu:	28.571% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.003
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.031	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.728
HLM stability:	0.062 ? 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):

2.195

Half-life (T1/2):

2.65

ADMET: Toxicity

hERG Blockers:	0.008	hERG Blockers (10um):	0.08
Human Hepatotoxicity (H-HT):	0.678	Drug-induced Liver Injury (DILI):	0.9
AMES Toxicity:	0.915	Rat Oral Acute Toxicity:	0.057
Maximum Recommended Daily Dose:	0.498	Skin Sensitization:	1.0
Carcinogencity:	0.636	Eye Corrosion:	0.0
Eye Irritation:	0.098	Respiratory Toxicity:	0.012
Drug-induced Neurotoxicity:	0.103	Ototoxicity:	0.967
Hematotoxicity:	0.214	Drug-induced Nephrotoxicity:	0.941
Genotoxicity:	0.987	RPMI-8226 Immunitoxicity:	0.14
A549 Cytotoxicity:	0.137	Hek293 Cytotoxicity:	0.336
BCF:	0.466 ? 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:	3.192 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.808 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.956 ? 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
NPO22304	Morinda morindoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12542353]
NPO6568	Prismatomeris tetrandra	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17665951]
NPO22304	Morinda morindoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20149652]
NPO22304	Morinda morindoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7775983]
NPO22304	Morinda morindoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6568	Prismatomeris tetrandra	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22304	Morinda morindoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6568	Prismatomeris tetrandra	Species	Rubiaceae	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	2

Activity Type	# Activity
Organism	1
Others	1

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
NPT992	Organism	Entamoeba histolytica	Entamoeba histolytica	IC50	=	4.3	ug.mL-1	PubChem BioAssay data set
NPT610	Others	Molecular identity unknown	n.a.	IC50	=	58000.0	nM	PMID[12542353]

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
-	Artemia	LD50	=	224.0	nM	PMID[19046886]
-	Artemia	LD50	=	380.0	ng/ml	PMID[11421746]

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 NPC475539 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	13206
0.1-0.2	32767
0.2-0.3	3354
0.3-0.4	425
0.4-0.5	85
0.5-0.6	9
0.6-0.7	4
0.7-0.8	0
0.8-0.85	4
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	NPC143246
0.8481	Intermediate Similarity	NPC286919
0.8481	Intermediate Similarity	NPC475663
0.8148	Intermediate Similarity	NPC474268
0.8148	Intermediate Similarity	NPC119773
0.7821	Intermediate Similarity	NPC474620
0.7654	Intermediate Similarity	NPC475378
0.7	Intermediate Similarity	NPC469384
0.6818	Remote Similarity	NPC63304
0.68	Remote Similarity	NPC254538
0.6744	Remote Similarity	NPC475528
0.6667	Remote Similarity	NPC180586
0.5532	Remote Similarity	NPC240592
0.5532	Remote Similarity	NPC117346
0.5326	Remote Similarity	NPC96599
0.5269	Remote Similarity	NPC31745
0.5269	Remote Similarity	NPC220936
0.5244	Remote Similarity	NPC475851
0.5244	Remote Similarity	NPC475924
0.5053	Remote Similarity	NPC202391
0.5053	Remote Similarity	NPC296659

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475539 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5204
0.1-0.2	3871
0.2-0.3	74
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