NPASS Compound

Natural Product: NPC88013

Natural Product ID	NPC88013
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Caseanigrescen B
IUPAC Name	[(1S,3R,5R,6aS,7S,8S,9R,10R,10aS)-1,3-diacetyloxy-9,10-dihydroxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] butanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL425815
PubChem CID	16109794
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 77 79 0 0 0 0 0 0 0 0999 V2000 6.2454 4.5871 -0.1838 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8454 3.9738 -0.4150 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9678 2.9313 -1.4654 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8007 2.0879 -1.7164 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6727 1.4268 -2.7276 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7585 2.0698 -0.6831 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6955 1.1493 -1.0261 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2409 -0.0966 -0.2578 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3858 -1.0510 -0.0686 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5637 -2.3972 0.6466 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4060 -2.3318 1.7491 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3293 -3.2204 2.2036 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4993 -4.2664 1.5611 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0951 -2.9186 3.4455 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2563 -2.3253 1.3063 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4821 -2.2498 0.0866 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0133 -0.9769 -0.5772 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5532 0.3136 -0.1261 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4840 1.4428 -0.2672 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8884 0.7989 -0.5821 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0476 2.2864 -0.5209 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1222 0.1309 -0.0539 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3685 -0.0179 1.3536 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5181 1.0317 2.3532 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5946 2.2895 2.2491 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2026 0.4735 3.8320 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2870 -0.8236 3.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9920 0.5167 -2.1219 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4085 0.7344 -2.5664 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5372 -0.8236 -2.5022 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1230 -1.1922 -2.0293 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0019 -2.5547 -2.2953 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4575 -0.8314 -3.9255 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7798 -2.5802 0.2294 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1955 -3.8732 -0.1595 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3729 -4.6728 -0.5981 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6631 -4.2270 -0.0136 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5020 4.4492 0.8910 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3041 5.5796 -0.5701 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9678 3.9404 -0.7746 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3524 3.6880 0.5003 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2476 4.8464 -0.8424 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2968 3.3678 -2.4490 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8103 2.2350 -1.1144 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7599 0.9218 -2.0526 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2513 -0.1638 0.0746 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6373 -3.2276 0.0034 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7559 -1.9357 3.8642 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8761 -3.6808 4.2548 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1793 -2.8441 3.2808 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0646 -3.0883 -0.4941 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6874 0.1944 1.0115 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0559 2.4116 -0.5681 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8503 1.6575 0.8075 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7067 2.7650 -1.4847 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1517 2.5095 -0.5353 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6472 2.7897 0.3545 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4388 -0.7625 -0.6782 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9657 0.8757 -0.4051 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1297 -0.8407 1.5824 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3816 -0.5843 1.8002 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7128 2.7461 3.3485 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5988 3.1384 1.6453 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0199 1.1138 4.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3825 -1.7845 3.5399 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3486 -1.0286 5.0329 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4265 1.3469 -2.6393 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3594 0.9060 -3.6983 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0818 -0.1291 -2.4729 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8696 1.6794 -2.2144 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2791 -1.5929 -2.2438 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5506 -0.6995 -2.7095 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9797 -2.8094 -2.3492 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9577 -0.0118 -4.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7942 -4.6269 0.9925 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2102 -3.2614 -0.0502 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9333 -4.9041 -0.8476 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 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 10 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 6 20 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 20 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 16 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 19 7 1 0 17 9 1 6 31 17 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 0 2 42 1 0 3 43 1 0 3 44 1 0 7 45 1 6 8 46 1 0 10 47 1 6 14 48 1 0 14 49 1 0 14 50 1 0 16 51 1 6 18 52 1 1 19 53 1 0 19 54 1 0 21 55 1 0 21 56 1 0 21 57 1 0 22 58 1 0 22 59 1 0 23 60 1 0 23 61 1 0 25 62 1 0 25 63 1 0 26 64 1 0 27 65 1 0 27 66 1 0 28 67 1 6 29 68 1 0 29 69 1 0 29 70 1 0 30 71 1 6 31 72 1 6 32 73 1 0 33 74 1 0 37 75 1 0 37 76 1 0 37 77 1 0 M END

Standard InCHIKey	FACSSBRLFWVHQA-OISZFCHFSA-N
Standard InCHI	InChI=1S/C28H40O9/c1-8-10-22(31)36-19-13-20-25(34-17(5)29)37-26(35-18(6)30)28(20)21(14-19)27(7,12-11-15(3)9-2)16(4)23(32)24(28)33/h9,13,16,19,21,23-26,32-33H,2-3,8,10-12,14H2,1,4-7H3/t16-,19+,21+,23-,24+,25+,26-,27-,28-/m1/s1
SMILES	CCCC(=O)O[C@H]1C=C2[C@@H](OC(=O)C)O[C@H]([C@]32[C@@H](C1)[C@](C)(CCC(=C)C=C)[C@H](C)[C@H]([C@@H]3O)O)OC(=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
NPO31135	Casearia nigrescens	Species	Salicaceae	Eukaryota	n.a.	flower	n.a.	PMID[17315961]
NPO31135	Casearia nigrescens	Species	Salicaceae	Eukaryota	leaves and flowers	Zahamena region of Madagascar, Toamasina, 3 km northeast of Nosivola (1741'01?S, 4838'28?)	2001-NOV	PMID[17315961]
NPO31135	Casearia nigrescens	Species	Salicaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17315961]
NPO31135	Casearia nigrescens	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	1

Activity Type	# Activity
Cell line	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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	830.0	nM	PMID[17315961]

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 NPC88013 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	19085
0.1-0.2	26835
0.2-0.3	3794
0.3-0.4	24
0.4-0.5	42
0.5-0.6	55
0.6-0.7	17
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
0.8594	High Similarity	NPC125423
0.7692	Intermediate Similarity	NPC7644
0.7576	Intermediate Similarity	NPC217921
0.7576	Intermediate Similarity	NPC135015
0.7121	Intermediate Similarity	NPC479943
0.6957	Remote Similarity	NPC48548
0.6912	Remote Similarity	NPC311223
0.6912	Remote Similarity	NPC479940
0.6901	Remote Similarity	NPC127933
0.6812	Remote Similarity	NPC475889
0.6812	Remote Similarity	NPC7613
0.6812	Remote Similarity	NPC479942
0.6761	Remote Similarity	NPC119550
0.6667	Remote Similarity	NPC128795
0.6667	Remote Similarity	NPC40728
0.6479	Remote Similarity	NPC479941
0.6338	Remote Similarity	NPC238397
0.6232	Remote Similarity	NPC479935
0.6232	Remote Similarity	NPC481019
0.6197	Remote Similarity	NPC201880
0.6164	Remote Similarity	NPC471363
0.6111	Remote Similarity	NPC473545
0.5915	Remote Similarity	NPC472186
0.589	Remote Similarity	NPC609715
0.5875	Remote Similarity	NPC316708
0.5857	Remote Similarity	NPC481020
0.5854	Remote Similarity	NPC470026
0.5833	Remote Similarity	NPC488649
0.5753	Remote Similarity	NPC134270
0.5753	Remote Similarity	NPC481017
0.5733	Remote Similarity	NPC488964
0.5733	Remote Similarity	NPC184512
0.5733	Remote Similarity	NPC472187
0.5714	Remote Similarity	NPC171598
0.5694	Remote Similarity	NPC488236
0.5679	Remote Similarity	NPC486751
0.5634	Remote Similarity	NPC479934
0.5625	Remote Similarity	NPC87630
0.5616	Remote Similarity	NPC471366
0.5616	Remote Similarity	NPC476800
0.5616	Remote Similarity	NPC488237
0.5556	Remote Similarity	NPC479936
0.5556	Remote Similarity	NPC318917
0.5556	Remote Similarity	NPC602188
0.5541	Remote Similarity	NPC479497
0.5541	Remote Similarity	NPC81567
0.5541	Remote Similarity	NPC488652
0.5479	Remote Similarity	NPC479937
0.5467	Remote Similarity	NPC330003
0.5467	Remote Similarity	NPC470321
0.5467	Remote Similarity	NPC264867
0.5467	Remote Similarity	NPC473207
0.5395	Remote Similarity	NPC488963
0.5352	Remote Similarity	NPC472189
0.5342	Remote Similarity	NPC479939
0.5333	Remote Similarity	NPC316974
0.5333	Remote Similarity	NPC329623
0.5333	Remote Similarity	NPC609711
0.5325	Remote Similarity	NPC252296
0.5278	Remote Similarity	NPC481018
0.527	Remote Similarity	NPC472188
0.5256	Remote Similarity	NPC488221
0.5256	Remote Similarity	NPC488220
0.5256	Remote Similarity	NPC488216
0.5244	Remote Similarity	NPC179128
0.52	Remote Similarity	NPC479938
0.5135	Remote Similarity	NPC88507
0.5135	Remote Similarity	NPC471362
0.5135	Remote Similarity	NPC471372
0.5135	Remote Similarity	NPC488659
0.5135	Remote Similarity	NPC604149
0.5132	Remote Similarity	NPC488654
0.5132	Remote Similarity	NPC479491
0.5114	Remote Similarity	NPC481026
0.507	Remote Similarity	NPC476802
0.5065	Remote Similarity	NPC488658
0.5065	Remote Similarity	NPC488655

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC88013 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7078
0.1-0.2	2012
0.2-0.3	60
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