NPASS Compound

Natural Product: NPC157816

Natural Product ID	NPC157816
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Khainaoside C
IUPAC Name	[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[4-[(E)-3-hydroxyprop-1-enyl]-2-methoxyphenoxy]oxan-2-yl]methyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1087168
PubChem CID	44606239
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0004165] Phenolic 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 64 66 0 0 0 0 0 0 0 0999 V2000 8.9208 2.3346 -2.6933 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0990 1.5826 -1.5492 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7706 1.1701 -1.0012 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6725 1.5423 -1.6239 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3827 1.1508 -1.1053 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2474 1.5709 -1.8046 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9856 1.2542 -1.3973 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7558 0.4853 -0.2481 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8577 0.0649 0.4497 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1497 0.4017 0.0138 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7188 -0.6972 1.5937 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8764 -1.1099 2.2833 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4691 0.2243 0.0737 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8490 -0.4635 1.0781 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0578 -1.4731 0.5320 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5693 -2.2853 1.3979 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6811 -3.0414 0.7189 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6952 -2.2876 0.1636 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6235 -1.3797 -0.8590 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5324 -1.1544 -1.4162 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8066 -0.6504 -1.3297 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9716 -0.8609 -0.7679 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1976 -0.1847 -1.1677 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3628 -0.5130 -0.4762 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5372 0.1041 -0.8251 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5662 1.0253 -1.8334 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4044 1.3403 -2.5093 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2084 0.7400 -2.1850 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4045 2.2808 -3.5471 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.7598 1.6295 -2.1628 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1386 -1.6670 2.6303 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4927 -0.4063 3.0704 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1697 0.4147 1.8401 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3746 1.6458 2.1490 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3329 0.2833 3.9415 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0817 -2.5853 3.6770 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1068 3.2829 -2.5499 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6069 2.2230 -0.7921 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6970 0.6604 -1.7444 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8038 0.5724 -0.0981 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7677 2.1379 -2.5168 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3860 2.1686 -2.7004 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1522 1.6187 -1.9954 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0059 0.0563 0.5845 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5579 -1.7250 1.6521 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5437 -1.6547 3.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3827 -0.1735 2.6460 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5014 -0.9424 1.8316 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1817 -3.0623 1.7357 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1375 -3.8008 1.4220 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2743 -3.6872 -0.1203 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7097 0.0491 -2.1296 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9734 -1.5978 0.0462 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2971 -1.2505 0.3192 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4270 -0.1661 -0.2757 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3293 1.0170 -2.7390 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3016 2.6088 -3.8734 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1764 2.3537 -1.5917 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2341 -1.4475 2.4739 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4965 -0.6335 3.5525 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0876 0.4715 1.2326 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2063 1.7465 1.5931 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9296 0.8400 3.3542 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1703 -2.1517 4.5630 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 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 8 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 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 26 30 1 0 16 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 32 35 1 0 31 36 1 0 10 5 1 0 33 14 1 0 28 23 1 0 1 37 1 0 2 38 1 0 2 39 1 0 3 40 1 0 4 41 1 0 6 42 1 0 7 43 1 0 10 44 1 0 12 45 1 0 12 46 1 0 12 47 1 0 14 48 1 1 16 49 1 1 17 50 1 0 17 51 1 0 21 52 1 0 22 53 1 0 24 54 1 0 25 55 1 0 28 56 1 0 29 57 1 0 30 58 1 0 31 59 1 6 32 60 1 1 33 61 1 6 34 62 1 0 35 63 1 0 36 64 1 0 M END

Standard InCHIKey	OVXNLDIJUODSJZ-WNTHUPNMSA-N
Standard InCHI	InChI=1S/C25H28O11/c1-33-19-12-14(3-2-10-26)5-8-18(19)35-25-24(32)23(31)22(30)20(36-25)13-34-21(29)9-6-15-4-7-16(27)17(28)11-15/h2-9,11-12,20,22-28,30-32H,10,13H2,1H3/b3-2+,9-6+/t20-,22-,23+,24-,25-/m1/s1
SMILES	OC/C=C/c1ccc(c(c1)OC)O[C@@H]1O[C@H](COC(=O)/C=C/c2ccc(c(c2)O)O)[C@H]([C@@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	504.16	Volume:	488.251 ? Van der Waals volume.
Dense:	1.033	LogP:	1.463 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.838 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.592 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	21.0
TPSA:	175.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.16	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.967	Fsp³:	0.32
MCE-18:	69.364 ? 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:	0.756	Fluc inhibitor:	0.999 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.254 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.885 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.154	Promiscuous compounds:	0.255

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.104	MDCK Permeability:	-5.369
Pgp-inhibitor:	0.014	Pgp-substrate:	0.003
PAMPA:	0.758 ? 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):	0.853
20% Bioavailability (F20%):	0.998	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.0
Plasma Protein Binding (PPB):	79.165%	Volume Distribution (VD):	-0.429
Fu:	18.35% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.073
BSEP inhibitor:	0.888

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:	0.0	CYP2D6-substrate:	0.014
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.995
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.548 ? 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):

4.473

Half-life (T1/2):

3.189

ADMET: Toxicity

hERG Blockers:	0.088	hERG Blockers (10um):	0.353
Human Hepatotoxicity (H-HT):	0.733	Drug-induced Liver Injury (DILI):	0.806
AMES Toxicity:	0.905	Rat Oral Acute Toxicity:	0.005
Maximum Recommended Daily Dose:	0.163	Skin Sensitization:	1.0
Carcinogencity:	0.143	Eye Corrosion:	0.0
Eye Irritation:	0.344	Respiratory Toxicity:	0.008
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.939
Hematotoxicity:	0.043	Drug-induced Nephrotoxicity:	0.242
Genotoxicity:	0.557	RPMI-8226 Immunitoxicity:	0.043
A549 Cytotoxicity:	0.548	Hek293 Cytotoxicity:	0.264
BCF:	0.597 ? 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:	3.31 ? 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:	4.382 ? 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
NPO25391	Vitex glabrata	Species	Lamiaceae	Eukaryota	leaves	Chantaburi Province, Thailand	2007-Nov	PMID[19943620]
NPO25391	Vitex glabrata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25391	Vitex glabrata	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

Activity Type	# Activity
Activity	6
Inhibition	1

Activity Type	# Activity
Cell line	7

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
NPT83	Cell line	MCF7	Homo sapiens	Activity	=	4.0	uM	PMID[25819096]
NPT83	Cell line	MCF7	Homo sapiens	Activity	=	5.0	uM	PMID[16472241]
NPT396	Cell line	T47D	Homo sapiens	Activity	<	0.1	uM	PMID[20000782]
NPT396	Cell line	T47D	Homo sapiens	Activity	>	100.0	uM	PMID[8988604]
NPT396	Cell line	T47D	Homo sapiens	Inhibition	>	90.0	%	PMID[12105963]

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 NPC157816 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	13299
0.1-0.2	30951
0.2-0.3	4309
0.3-0.4	984
0.4-0.5	256
0.5-0.6	37
0.6-0.7	14
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
0.7089	Intermediate Similarity	NPC471405
0.6962	Remote Similarity	NPC10205
0.6753	Remote Similarity	NPC157898
0.675	Remote Similarity	NPC291296
0.6667	Remote Similarity	NPC476867
0.6628	Remote Similarity	NPC11411
0.6627	Remote Similarity	NPC476868
0.6585	Remote Similarity	NPC476864
0.6471	Remote Similarity	NPC476865
0.6375	Remote Similarity	NPC137813
0.6364	Remote Similarity	NPC133984
0.6322	Remote Similarity	NPC488081
0.6163	Remote Similarity	NPC476870
0.6027	Remote Similarity	NPC248355
0.6023	Remote Similarity	NPC479767
0.5934	Remote Similarity	NPC476871
0.593	Remote Similarity	NPC476866
0.5862	Remote Similarity	NPC488082
0.5802	Remote Similarity	NPC291153
0.575	Remote Similarity	NPC229784
0.5747	Remote Similarity	NPC476869
0.5696	Remote Similarity	NPC470572
0.5568	Remote Similarity	NPC289811
0.5488	Remote Similarity	NPC287597
0.5455	Remote Similarity	NPC204937
0.5455	Remote Similarity	NPC134905
0.5412	Remote Similarity	NPC219677
0.5395	Remote Similarity	NPC476873
0.5393	Remote Similarity	NPC226005
0.5354	Remote Similarity	NPC488385
0.5326	Remote Similarity	NPC83743
0.5312	Remote Similarity	NPC44507
0.5301	Remote Similarity	NPC186406
0.53	Remote Similarity	NPC81042
0.5256	Remote Similarity	NPC302378
0.5217	Remote Similarity	NPC147224
0.5213	Remote Similarity	NPC300262
0.5185	Remote Similarity	NPC488078
0.5161	Remote Similarity	NPC308178
0.5149	Remote Similarity	NPC214621
0.5149	Remote Similarity	NPC34267
0.5149	Remote Similarity	NPC603856
0.5143	Remote Similarity	NPC139571
0.5128	Remote Similarity	NPC55040
0.5104	Remote Similarity	NPC125823
0.5104	Remote Similarity	NPC7145
0.5104	Remote Similarity	NPC143480
0.5104	Remote Similarity	NPC469654
0.5098	Remote Similarity	NPC599948
0.5054	Remote Similarity	NPC262182
0.5052	Remote Similarity	NPC7191
0.5052	Remote Similarity	NPC149873

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC157816 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4322
0.1-0.2	4700
0.2-0.3	113
0.3-0.4	14
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