NPASS Compound

Natural Product: NPC281277

Natural Product ID	NPC281277
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(S)-1'-Methylhexyl Caffeate
IUPAC Name	[(2S)-heptan-2-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms	(S)-1'-Methylhexyl Caffeate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1641897
PubChem CID	50901245
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

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 42 42 0 0 0 0 0 0 0 0999 V2000 5.0848 -1.2100 -1.7942 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7892 0.2638 -1.9894 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9374 0.9456 -0.6463 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0066 0.3928 0.3758 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5418 0.5213 0.0304 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7681 -0.0818 1.1742 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1139 -1.5383 1.3835 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3822 0.0314 1.0409 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4637 0.6803 1.8837 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0043 1.2474 2.8932 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8973 0.6871 1.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3482 0.0727 0.4890 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7433 0.0255 0.0980 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0789 -0.6596 -1.0702 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3854 -0.7309 -1.4794 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3869 -0.1360 -0.7575 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0611 0.5319 0.3812 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7374 0.6165 0.8154 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0593 1.1361 1.1186 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7012 -0.2262 -1.1986 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7645 -1.6012 -2.5970 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6190 -1.4085 -0.8415 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1534 -1.8177 -1.8843 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7517 0.3897 -2.3385 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5223 0.6848 -2.7122 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8288 2.0482 -0.7758 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0000 0.8005 -0.3517 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2451 0.8242 1.3639 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2211 -0.7017 0.4654 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3737 -0.0216 -0.9219 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3109 1.5946 -0.0208 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0760 0.4531 2.0963 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6150 -1.9606 0.4813 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7410 -1.6937 2.2974 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1796 -2.1447 1.5703 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6011 1.1964 2.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5998 -0.4251 -0.1351 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2891 -1.1343 -1.6483 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6372 -1.2637 -2.3858 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5238 1.1524 1.7181 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0800 2.0928 1.4040 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4364 0.3670 -0.8240 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 6 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 16 20 1 0 18 13 1 0 1 21 1 0 1 22 1 0 1 23 1 0 2 24 1 0 2 25 1 0 3 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 5 30 1 0 5 31 1 0 6 32 1 1 7 33 1 0 7 34 1 0 7 35 1 0 11 36 1 0 12 37 1 0 14 38 1 0 15 39 1 0 18 40 1 0 19 41 1 0 20 42 1 0 M END

Standard InCHIKey	NCSRSZJMEGATGP-OANVXVOSSA-N
Standard InCHI	InChI=1S/C16H22O4/c1-3-4-5-6-12(2)20-16(19)10-8-13-7-9-14(17)15(18)11-13/h7-12,17-18H,3-6H2,1-2H3/b10-8+/t12-/m0/s1
SMILES	CCCCC[C@H](C)OC(=O)/C=C/c1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO20527	Piper sanguineispicum	Species	Piperaceae	Eukaryota	leaves	n.a.	n.a.	PMID[20954722]
NPO20527	Piper sanguineispicum	Species	Piperaceae	Eukaryota	n.a.	leaf	n.a.	PMID[20954722]
NPO20527	Piper sanguineispicum	Species	Piperaceae	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	3

Activity Type	# Activity
Cell line	2
Organism	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
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	89800.0	nM	PMID[20954722]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	10600.0	nM	PMID[20954722]
NPT634	Organism	Leishmania amazonensis	Leishmania amazonensis	IC50	=	10000.0	nM	PMID[20954722]

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 NPC281277 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	8849
0.1-0.2	35299
0.2-0.3	5005
0.3-0.4	503
0.4-0.5	134
0.5-0.6	48
0.6-0.7	15
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.975	High Similarity	NPC309434
0.925	High Similarity	NPC233669
0.7174	Intermediate Similarity	NPC474275
0.6939	Remote Similarity	NPC470849
0.6809	Remote Similarity	NPC224208
0.6809	Remote Similarity	NPC41661
0.6667	Remote Similarity	NPC470848
0.6531	Remote Similarity	NPC203124
0.6531	Remote Similarity	NPC607366
0.6458	Remote Similarity	NPC328593
0.6458	Remote Similarity	NPC147192
0.6429	Remote Similarity	NPC226250
0.6383	Remote Similarity	NPC33749
0.6364	Remote Similarity	NPC95381
0.6226	Remote Similarity	NPC26241
0.6182	Remote Similarity	NPC474875
0.6042	Remote Similarity	NPC474967
0.6	Remote Similarity	NPC219428
0.5769	Remote Similarity	NPC65791
0.5769	Remote Similarity	NPC168799
0.5741	Remote Similarity	NPC258469
0.5741	Remote Similarity	NPC43158
0.5741	Remote Similarity	NPC155209
0.5741	Remote Similarity	NPC610147
0.5738	Remote Similarity	NPC610018
0.5714	Remote Similarity	NPC261453
0.569	Remote Similarity	NPC319628
0.566	Remote Similarity	NPC488563
0.566	Remote Similarity	NPC474895
0.5645	Remote Similarity	NPC603702
0.5625	Remote Similarity	NPC217472
0.5625	Remote Similarity	NPC150610
0.5517	Remote Similarity	NPC600402
0.5439	Remote Similarity	NPC13818
0.5424	Remote Similarity	NPC277315
0.5424	Remote Similarity	NPC472016
0.5424	Remote Similarity	NPC192831
0.54	Remote Similarity	NPC275519
0.54	Remote Similarity	NPC217052
0.54	Remote Similarity	NPC329344
0.54	Remote Similarity	NPC237506
0.54	Remote Similarity	NPC32626
0.5323	Remote Similarity	NPC483141
0.5294	Remote Similarity	NPC147654
0.5254	Remote Similarity	NPC295492
0.5254	Remote Similarity	NPC303683
0.5254	Remote Similarity	NPC274891
0.5246	Remote Similarity	NPC205751
0.5246	Remote Similarity	NPC206095
0.5246	Remote Similarity	NPC35702
0.5246	Remote Similarity	NPC224389
0.5185	Remote Similarity	NPC106406
0.5167	Remote Similarity	NPC611548
0.5094	Remote Similarity	NPC263386
0.5094	Remote Similarity	NPC141791
0.5094	Remote Similarity	NPC273741
0.5094	Remote Similarity	NPC608423
0.5094	Remote Similarity	NPC611337
0.5082	Remote Similarity	NPC471027
0.5082	Remote Similarity	NPC37250
0.5082	Remote Similarity	NPC142703
0.5082	Remote Similarity	NPC152942
0.5082	Remote Similarity	NPC9991
0.5082	Remote Similarity	NPC302857
0.5082	Remote Similarity	NPC477333
0.5082	Remote Similarity	NPC600892

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC281277 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3064
0.1-0.2	5840
0.2-0.3	234
0.3-0.4	11
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