NPASS Compound

Natural Product: NPC116292

Natural Product ID	NPC116292
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Casearborin D
IUPAC Name	[(1S,3R,5R,6aS,7R,8R,10S,10aS)-1,3-diacetyloxy-10-hydroxy-7,8-dimethyl-7-[(2E)-3-methylpenta-2,4-dienyl]-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 4-hydroxybenzoate
Synonyms	Casearborin D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL500119
PubChem CID	10460317
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

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 78 81 0 0 0 0 0 0 0 0999 V2000 -6.9154 0.5831 1.3124 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6335 0.3440 1.3337 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6225 1.3402 1.0379 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3393 1.0138 1.0800 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2590 1.9256 0.8018 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2646 1.4877 -0.2865 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2698 2.6440 -0.3530 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8512 1.4498 -1.6590 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5007 2.7449 -2.0394 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6302 0.2220 -1.9771 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8493 -1.0334 -1.7559 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8577 -1.0179 -0.6426 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4120 -1.6821 -1.1425 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5796 -1.1209 -1.1591 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7058 0.2994 -0.6412 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7952 0.2866 0.5528 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6697 0.1892 0.1588 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0283 0.4621 -0.1644 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8893 1.4322 -0.6477 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4495 2.1865 -1.5486 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2409 1.6199 -0.1801 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0211 2.6112 -0.7213 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3372 2.8163 -0.2868 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8466 2.0029 0.7011 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0715 0.9877 1.2667 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7780 0.8247 0.8043 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1418 2.1963 1.1364 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1053 -3.0394 -1.5172 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8564 -4.0425 -1.3454 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2391 -4.8677 -2.3646 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7177 -4.7361 -3.5101 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2659 -5.9131 -2.1161 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1558 -3.2868 -0.6655 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3081 -2.2341 0.2273 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5879 -2.3681 1.3923 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2308 -2.4066 2.6170 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4799 -2.3192 2.6502 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5008 -2.5481 3.9055 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6529 -2.1699 -1.7446 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0077 2.7504 0.7002 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6217 -0.2364 1.5519 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4101 1.5055 1.0832 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3159 -0.6737 1.5921 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1325 -0.0092 1.3428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6232 2.9558 0.6063 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6847 2.0624 1.7732 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6232 2.5410 0.2283 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7494 3.6097 -0.0006 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0352 2.9029 -1.3919 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9320 1.3864 -2.3345 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0619 3.1883 -2.9898 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3729 3.5341 -1.2995 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5791 2.5945 -2.3487 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9652 0.2913 -3.0337 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5572 0.1858 -1.3765 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2446 -1.1741 -2.7101 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4494 -1.6493 -1.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5140 1.0311 -1.4042 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0116 -0.7162 1.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0206 0.9775 1.3553 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1249 -0.0708 1.1781 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6853 3.2862 -1.5000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9801 3.5832 -0.6869 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5016 0.3667 2.0405 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2025 0.0289 1.2628 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6427 3.0632 1.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4673 -3.0407 -2.5494 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0756 -6.8104 -2.7447 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2808 -6.2212 -1.0447 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2871 -5.5724 -2.3585 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3849 -2.1554 0.4504 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1447 -3.1337 4.5828 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2679 -1.5907 4.3701 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4693 -3.0876 3.7332 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4982 -1.9242 -2.2135 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4136 3.4440 1.3603 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8513 2.9640 -0.3753 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0596 2.9289 0.9154 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 6 5 1 1 6 7 1 0 6 8 1 0 8 9 1 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 15 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 24 27 1 0 13 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 28 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 11 39 1 0 3 40 1 0 17 6 1 0 26 21 1 0 17 12 1 0 34 12 1 0 1 41 1 0 1 42 1 0 2 43 1 0 4 44 1 0 5 45 1 0 5 46 1 0 7 47 1 0 7 48 1 0 7 49 1 0 8 50 1 6 9 51 1 0 9 52 1 0 9 53 1 0 10 54 1 0 10 55 1 0 11 56 1 6 14 57 1 0 15 58 1 6 16 59 1 0 16 60 1 0 17 61 1 1 22 62 1 0 23 63 1 0 25 64 1 0 26 65 1 0 27 66 1 0 28 67 1 6 32 68 1 0 32 69 1 0 32 70 1 0 34 71 1 1 38 72 1 0 38 73 1 0 38 74 1 0 39 75 1 0 40 76 1 0 40 77 1 0 40 78 1 0 M END

Standard InCHIKey	BTSDTWZLDJUDMR-VICZHGOXSA-N
Standard InCHI	InChI=1S/C31H38O9/c1-7-17(2)12-13-30(6)18(3)14-26(35)31-24(28(37-19(4)32)40-29(31)38-20(5)33)15-23(16-25(30)31)39-27(36)21-8-10-22(34)11-9-21/h7-12,15,18,23,25-26,28-29,34-35H,1,13-14,16H2,2-6H3/b17-12+/t18-,23+,25+,26+,28+,29-,30-,31-/m1/s1
SMILES	C=C/C(=C/C[C@]1(C)[C@H](C)C[C@@H]([C@@]23C(=C[C@@H](C[C@@H]12)OC(=O)c1ccc(cc1)O)[C@@H](OC(=O)C)O[C@H]3OC(=O)C)O)/C

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
NPO28776	Casearia arborea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10843580]
NPO28776	Casearia arborea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28776	Casearia arborea	Species	Salicaceae	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
Kd	1
IC50	3
Inhibition	1

Activity Type	# Activity
Individual protein	1
Cell line	3
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT5536	Individual protein	Sarcoplasmic/endoplasmic reticulum calcium ATP-ase	Oryctolagus cuniculus	Kd	=	2000.0	nM	PMID[15568762]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT390	Cell line	LOX IMVI	Homo sapiens	IC50	=	290.0	nM	PMID[25946116]
NPT374	Cell line	SF-539	Homo sapiens	IC50	=	290.0	nM	PMID[18955526]
NPT404	Cell line	CCRF-CEM	Homo sapiens	IC50	=	1100.0	nM	PMID[20430633]
NPT2	Others	Unspecified	n.a.	Inhibition	=	23.84	%	PMID[12662097]

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 NPC116292 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	7416
0.1-0.2	38358
0.2-0.3	3934
0.3-0.4	75
0.4-0.5	23
0.5-0.6	19
0.6-0.7	25
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
0.8108	Intermediate Similarity	NPC87630
0.7632	Intermediate Similarity	NPC179128
0.7286	Intermediate Similarity	NPC602188
0.7273	Intermediate Similarity	NPC208293
0.7123	Intermediate Similarity	NPC330003
0.7123	Intermediate Similarity	NPC470321
0.7123	Intermediate Similarity	NPC264867
0.7123	Intermediate Similarity	NPC473207
0.6986	Remote Similarity	NPC201880
0.6986	Remote Similarity	NPC81567
0.6986	Remote Similarity	NPC329623
0.6986	Remote Similarity	NPC488652
0.6986	Remote Similarity	NPC609711
0.6875	Remote Similarity	NPC162569
0.6875	Remote Similarity	NPC35160
0.6806	Remote Similarity	NPC488659
0.6806	Remote Similarity	NPC604149
0.6711	Remote Similarity	NPC488964
0.6711	Remote Similarity	NPC184512
0.6667	Remote Similarity	NPC267469
0.6667	Remote Similarity	NPC488658
0.6667	Remote Similarity	NPC488655
0.6667	Remote Similarity	NPC609715
0.6533	Remote Similarity	NPC134270
0.6533	Remote Similarity	NPC488660
0.6533	Remote Similarity	NPC488657
0.6533	Remote Similarity	NPC488654
0.6533	Remote Similarity	NPC609880
0.6364	Remote Similarity	NPC320734
0.6282	Remote Similarity	NPC252296
0.6053	Remote Similarity	NPC488653
0.6053	Remote Similarity	NPC488656
0.6	Remote Similarity	NPC109376
0.5897	Remote Similarity	NPC479491
0.5843	Remote Similarity	NPC100420
0.5641	Remote Similarity	NPC479943
0.5625	Remote Similarity	NPC475889
0.5625	Remote Similarity	NPC7613
0.5625	Remote Similarity	NPC479942
0.55	Remote Similarity	NPC311223
0.55	Remote Similarity	NPC479940
0.55	Remote Similarity	NPC7644
0.55	Remote Similarity	NPC316974
0.55	Remote Similarity	NPC479497
0.5455	Remote Similarity	NPC486751
0.5402	Remote Similarity	NPC473399
0.5402	Remote Similarity	NPC473216
0.5366	Remote Similarity	NPC479941
0.5244	Remote Similarity	NPC238397
0.5176	Remote Similarity	NPC127933
0.5119	Remote Similarity	NPC471363
0.5059	Remote Similarity	NPC119550

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC116292 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4107
0.1-0.2	4984
0.2-0.3	59
0.3-0.4	0
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