NPASS Compound

Natural Product: NPC281798

Natural Product ID	NPC281798
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Kodemariosides A
IUPAC Name	[(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[(2Z)-2-[(4S,5R)-4-hydroxy-5-(2-methylprop-1-enyl)-2-oxooxolan-3-ylidene]ethoxy]oxan-2-yl]methyl (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1088521
PubChem CID	46833712
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0003002] Hydroxycinnamic acid esters [CHEMONTID:0000465] Coumaric acid esters

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 68 0 0 0 0 0 0 0 0999 V2000 7.9845 4.9260 -1.6503 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6728 4.5497 -1.0960 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9668 3.5813 -1.6678 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6347 3.1468 -1.1643 C 0 0 2 0 0 0 0 0 0 0 0 0 4.7319 1.6704 -0.8380 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3207 1.2390 -1.0204 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6169 0.3563 -0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2003 0.0210 -0.6626 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1621 -1.3334 -0.9894 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1198 -1.7813 -1.2855 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1489 -2.2876 -2.6726 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2905 -3.7563 -2.8351 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9867 -4.4806 -1.7354 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6021 -3.4069 -0.8234 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5381 -4.0292 0.1422 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1708 -3.0953 0.9631 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6342 -2.2381 1.8667 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3970 -2.2386 2.0412 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4822 -1.3123 2.6406 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7902 -1.2907 2.4766 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7193 -0.4308 3.1753 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0660 -0.5367 2.8847 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9609 0.2747 3.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5261 1.1972 4.4888 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1899 1.2930 4.7681 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2810 0.4893 4.1220 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4406 2.0120 5.1448 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5549 -2.6910 -0.3286 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0066 -5.2793 -2.2235 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9967 -4.3353 -2.9476 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1789 -1.6294 -3.3705 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8467 2.0400 -2.1426 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8962 1.7380 -2.9250 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6498 3.1948 -2.1745 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1868 1.4450 0.4529 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1242 5.2480 0.1082 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7972 4.2085 -1.3812 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2682 5.9744 -1.3794 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8812 4.8962 -2.7707 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3441 3.0646 -2.5372 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3272 3.6604 -0.2421 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3650 1.2093 -1.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1440 -0.1616 0.4444 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6640 0.0659 0.3430 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6862 0.6807 -1.3441 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7846 -0.8907 -1.1752 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7931 -1.9849 -3.2130 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7923 -4.0329 -3.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2857 -5.0816 -1.0981 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1391 -2.7307 -1.5532 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3674 -4.4954 -0.4730 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1039 -4.8843 0.7006 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0388 -0.6437 3.3483 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1719 -1.9932 1.7446 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4238 -1.2432 2.1548 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0110 0.1915 3.3128 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8547 2.0043 5.4993 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2444 0.5902 4.3644 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1373 2.5307 4.6443 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8173 -4.7492 -2.4374 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8659 -5.2743 -3.1866 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0013 -0.6625 -3.4161 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1219 1.1916 0.5180 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2194 4.5581 0.9855 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0983 5.5427 -0.1113 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6918 6.1895 0.3086 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 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 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 14 28 1 0 13 29 1 0 12 30 1 0 11 31 1 0 6 32 1 0 32 33 2 0 32 34 1 0 5 35 1 0 2 36 1 0 34 4 1 0 28 10 1 0 26 21 1 0 1 37 1 0 1 38 1 0 1 39 1 0 3 40 1 0 4 41 1 1 5 42 1 6 7 43 1 0 8 44 1 0 8 45 1 0 10 46 1 6 11 47 1 6 12 48 1 6 13 49 1 1 14 50 1 6 15 51 1 0 15 52 1 0 19 53 1 0 20 54 1 0 22 55 1 0 23 56 1 0 25 57 1 0 26 58 1 0 27 59 1 0 29 60 1 0 30 61 1 0 31 62 1 0 35 63 1 0 36 64 1 0 36 65 1 0 36 66 1 0 M END

Standard InCHIKey	KRHXGSVJPFGCQY-PBPOHICXSA-N
Standard InCHI	InChI=1S/C25H30O11/c1-13(2)11-17-20(28)16(24(32)35-17)9-10-33-25-23(31)22(30)21(29)18(36-25)12-34-19(27)8-5-14-3-6-15(26)7-4-14/h3-9,11,17-18,20-23,25-26,28-31H,10,12H2,1-2H3/b8-5+,16-9-/t17-,18-,20+,21-,22+,23-,25-/m1/s1
SMILES	CC(=C[C@@H]1[C@H](/C(=C/CO[C@H]2[C@@H]([C@H]([C@@H]([C@@H](COC(=O)/C=C/c3ccc(cc3)O)O2)O)O)O)/C(=O)O1)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.18	Volume:	490.888 ? Van der Waals volume.
Dense:	1.031	LogP:	2.385 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.656 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.626 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	22.0
TPSA:	172.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.182	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.654	Fsp³:	0.44
MCE-18:	74.556 ? 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:	0.745	Fluc inhibitor:	0.665 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.229 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.309 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.154	Promiscuous compounds:	0.264

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.788	MDCK Permeability:	-4.992
Pgp-inhibitor:	0.794	Pgp-substrate:	0.03
PAMPA:	0.938 ? 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):	0.552
20% Bioavailability (F20%):	0.954	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.012
Plasma Protein Binding (PPB):	83.084%	Volume Distribution (VD):	-0.347
Fu:	15.259% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.002
BSEP inhibitor:	0.961

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.026
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.063
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.555 ? 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):

3.475

Half-life (T1/2):

2.233

ADMET: Toxicity

hERG Blockers:	0.051	hERG Blockers (10um):	0.264
Human Hepatotoxicity (H-HT):	0.709	Drug-induced Liver Injury (DILI):	0.654
AMES Toxicity:	0.901	Rat Oral Acute Toxicity:	0.027
Maximum Recommended Daily Dose:	0.195	Skin Sensitization:	1.0
Carcinogencity:	0.138	Eye Corrosion:	0.0
Eye Irritation:	0.075	Respiratory Toxicity:	0.003
Drug-induced Neurotoxicity:	0.053	Ototoxicity:	0.882
Hematotoxicity:	0.164	Drug-induced Nephrotoxicity:	0.852
Genotoxicity:	0.592	RPMI-8226 Immunitoxicity:	0.17
A549 Cytotoxicity:	0.624	Hek293 Cytotoxicity:	0.426
BCF:	0.761 ? 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:	3.464 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.148 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.527 ? 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
NPO8538	Spiraea cantoniensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20329740]
NPO8538	Spiraea cantoniensis	Species	Rosaceae	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
Inhibition	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT671	Individual protein	Acidic alpha-glucosidase	Rattus norvegicus	Inhibition	=	15.0	%	PMID[25927586]

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 NPC281798 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	12798
0.1-0.2	32670
0.2-0.3	3687
0.3-0.4	552
0.4-0.5	119
0.5-0.6	23
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8873	High Similarity	NPC220942
0.6622	Remote Similarity	NPC288416
0.6282	Remote Similarity	NPC34293
0.6184	Remote Similarity	NPC479473
0.6184	Remote Similarity	NPC275721
0.6184	Remote Similarity	NPC479468
0.6184	Remote Similarity	NPC479474
0.5926	Remote Similarity	NPC252114
0.5696	Remote Similarity	NPC229784
0.5641	Remote Similarity	NPC470572
0.5625	Remote Similarity	NPC287597
0.5581	Remote Similarity	NPC235294
0.5556	Remote Similarity	NPC291153
0.5455	Remote Similarity	NPC471881
0.5385	Remote Similarity	NPC184633
0.5325	Remote Similarity	NPC52097
0.5233	Remote Similarity	NPC225307
0.5227	Remote Similarity	NPC138777
0.52	Remote Similarity	NPC476872
0.5172	Remote Similarity	NPC10205
0.5169	Remote Similarity	NPC476869
0.5169	Remote Similarity	NPC476866
0.5161	Remote Similarity	NPC300262
0.5114	Remote Similarity	NPC28637
0.5056	Remote Similarity	NPC246869
0.5056	Remote Similarity	NPC225384
0.5053	Remote Similarity	NPC125823
0.5053	Remote Similarity	NPC7145
0.5053	Remote Similarity	NPC143480
0.5052	Remote Similarity	NPC201148

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC281798 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5081
0.1-0.2	4010
0.2-0.3	56
0.3-0.4	2
0.4-0.5	1
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