NPASS Compound

Natural Product: NPC318917

Natural Product ID	NPC318917
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Caseargrewiin A
IUPAC Name	[(1R,3S,5S,6aR,7S,8S,10R,10aR)-1,3-diacetyloxy-10-methoxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 3-methylbutanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL515658
PubChem CID	11330035
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 82 84 0 0 0 0 0 0 0 0999 V2000 4.7719 -0.9528 -2.1195 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4274 -2.1504 -2.5182 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2128 -2.8699 -2.2492 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1306 -4.1013 -2.8091 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0883 -2.3744 -1.4417 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3961 -2.1605 0.0210 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2121 -1.7832 0.8281 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2354 -2.9863 0.6514 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5562 -1.7763 2.2908 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6456 -2.8435 2.4823 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9460 -0.5027 2.8880 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9069 0.7500 2.0602 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0280 0.7570 0.8823 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4290 -0.5785 0.5269 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8375 -0.7203 1.4108 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9123 0.2228 0.9933 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5156 -0.1020 -0.2407 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8919 -0.3404 -0.3529 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5678 -0.2538 0.6900 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5203 -0.6812 -1.6556 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0004 -0.8748 -1.4356 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6708 0.3497 -0.8942 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7176 -1.3320 -2.6652 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3192 1.5736 1.0020 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0565 1.7527 0.9522 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7255 3.0473 0.9052 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8436 2.7565 0.1691 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7093 1.4245 -0.3320 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8124 1.5271 -1.4038 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1139 1.2970 -2.7351 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2850 0.9712 -3.0470 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0536 1.4346 -3.7967 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0592 4.0815 0.3487 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4087 5.2211 1.0523 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0138 5.3425 2.2314 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2435 6.2448 0.3541 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2024 1.1454 1.7014 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7535 2.1611 2.4003 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1206 -0.3714 -1.5140 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7222 -0.4788 -2.3711 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2241 -2.6369 -3.1525 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2608 -4.7045 -2.6595 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9416 -4.4484 -3.3933 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7250 -1.3793 -1.8414 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2319 -3.1075 -1.5468 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6475 -3.2225 0.3798 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3063 -1.6122 0.2389 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1730 -3.3191 1.6026 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4921 -2.7465 -0.1356 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8155 -3.8727 0.2500 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6760 -2.2427 2.8399 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8387 -2.8442 3.5961 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2809 -3.8523 2.2583 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5934 -2.5569 2.0307 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3964 -0.3829 3.8543 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0151 -0.6021 3.2574 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5916 1.5309 2.7879 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1484 -0.5646 -0.5457 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5143 -0.3877 2.4329 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2507 -1.7230 1.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7367 0.2361 1.7648 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3480 0.1345 -2.4137 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1030 -1.6078 -2.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1013 -1.6767 -0.6588 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7019 0.3991 -1.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1582 1.2896 -1.2011 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7890 0.2954 0.2142 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1810 -0.4316 -3.1642 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6050 -1.9330 -2.3203 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0589 -1.8931 -3.3403 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0591 2.4150 1.0543 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0157 3.2626 1.9470 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7025 1.0886 -0.5406 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8367 1.9180 -3.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4593 2.0658 -4.5919 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1863 0.4499 -4.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1825 5.7859 -0.0152 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4017 7.1478 0.9609 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6692 6.5596 -0.5560 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8573 1.9578 3.4986 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3872 3.1747 2.2066 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8405 2.2105 2.0714 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 3 5 1 0 5 6 1 0 7 6 1 6 7 8 1 0 7 9 1 0 9 10 1 0 9 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 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 16 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 26 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 12 37 1 0 37 38 1 0 14 7 1 0 28 13 1 0 13 25 1 1 1 39 1 0 1 40 1 0 2 41 1 0 4 42 1 0 4 43 1 0 5 44 1 0 5 45 1 0 6 46 1 0 6 47 1 0 8 48 1 0 8 49 1 0 8 50 1 0 9 51 1 1 10 52 1 0 10 53 1 0 10 54 1 0 11 55 1 0 11 56 1 0 12 57 1 1 14 58 1 6 15 59 1 0 15 60 1 0 16 61 1 1 20 62 1 0 20 63 1 0 21 64 1 0 22 65 1 0 22 66 1 0 22 67 1 0 23 68 1 0 23 69 1 0 23 70 1 0 24 71 1 0 26 72 1 1 28 73 1 6 32 74 1 0 32 75 1 0 32 76 1 0 36 77 1 0 36 78 1 0 36 79 1 0 38 80 1 0 38 81 1 0 38 82 1 0 M END

Standard InCHIKey	OSFRHUJJEKKRCH-GTMUTZHESA-N
Standard InCHI	InChI=1S/C30H44O8/c1-10-18(4)11-12-29(8)19(5)14-25(34-9)30-23(27(35-20(6)31)38-28(30)36-21(7)32)15-22(16-24(29)30)37-26(33)13-17(2)3/h10,15,17,19,22,24-25,27-28H,1,4,11-14,16H2,2-3,5-9H3/t19-,22+,24+,25+,27+,28-,29-,30-/m0/s1
SMILES	C=CC(=C)CC[C@@]1(C)[C@@H](C)C[C@H]([C@]23[C@@H]1C[C@H](OC(=O)CC(C)C)C=C3[C@@H](O[C@@H]2OC(=O)C)OC(=O)C)OC

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
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	bark	n.a.	PMID[15730240]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	bark	in the campus of Khon Kaen University, Khon Kaen, Thailand	2001-SEP	PMID[15730240]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[17567069]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26516994]
NPO31460	Casearia grewiifolia	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	4
MIC	1

Activity Type	# Activity
Cell line	2
Organism	2
Non-molecular	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
NPT91	Cell line	KB	Homo sapiens	IC50	=	8.7	ug.mL-1	PMID[15730240]
NPT639	Cell line	NCI-H187	Homo sapiens	IC50	=	0.9	ug.mL-1	PMID[15730240]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	12.5	ug.mL-1	PMID[15730240]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	4.6	ug.mL-1	PMID[15730240]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	2.9	ug.mL-1	PMID[15730240]

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 NPC318917 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	22508
0.1-0.2	25375
0.2-0.3	1833
0.3-0.4	26
0.4-0.5	49
0.5-0.6	28
0.6-0.7	17
0.7-0.8	0
0.8-0.85	7
0.85-0.9	6
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9273	High Similarity	NPC171598
0.8947	High Similarity	NPC481019
0.875	High Similarity	NPC472189
0.8644	High Similarity	NPC471366
0.8644	High Similarity	NPC476800
0.8644	High Similarity	NPC488237
0.8596	High Similarity	NPC481018
0.8475	Intermediate Similarity	NPC472186
0.8448	Intermediate Similarity	NPC481020
0.8333	Intermediate Similarity	NPC488649
0.8305	Intermediate Similarity	NPC471362
0.8305	Intermediate Similarity	NPC471372
0.8197	Intermediate Similarity	NPC481017
0.8167	Intermediate Similarity	NPC472188
0.7869	Intermediate Similarity	NPC488236
0.7812	Intermediate Similarity	NPC472187
0.75	Intermediate Similarity	NPC473545
0.7097	Intermediate Similarity	NPC606965
0.6984	Remote Similarity	NPC132395
0.6984	Remote Similarity	NPC471364
0.6984	Remote Similarity	NPC600724
0.6875	Remote Similarity	NPC479936
0.6667	Remote Similarity	NPC473204
0.6567	Remote Similarity	NPC479940
0.6508	Remote Similarity	NPC603601
0.6462	Remote Similarity	NPC488651
0.6462	Remote Similarity	NPC488648
0.6377	Remote Similarity	NPC48548
0.6324	Remote Similarity	NPC471365
0.6212	Remote Similarity	NPC479934
0.6119	Remote Similarity	NPC479935
0.6119	Remote Similarity	NPC488235
0.6087	Remote Similarity	NPC128795
0.6029	Remote Similarity	NPC479943
0.6	Remote Similarity	NPC488962
0.5882	Remote Similarity	NPC479939
0.5857	Remote Similarity	NPC7644
0.5833	Remote Similarity	NPC488219
0.5797	Remote Similarity	NPC479937
0.5753	Remote Similarity	NPC488221
0.5753	Remote Similarity	NPC488220
0.5753	Remote Similarity	NPC488216
0.5714	Remote Similarity	NPC479938
0.5694	Remote Similarity	NPC488963
0.5606	Remote Similarity	NPC488650
0.5606	Remote Similarity	NPC481022
0.5556	Remote Similarity	NPC217921
0.5556	Remote Similarity	NPC88013
0.5556	Remote Similarity	NPC475889
0.5556	Remote Similarity	NPC7613
0.5556	Remote Similarity	NPC479942
0.5556	Remote Similarity	NPC135015
0.5479	Remote Similarity	NPC479941
0.5455	Remote Similarity	NPC486752
0.5342	Remote Similarity	NPC238397
0.5185	Remote Similarity	NPC486759
0.5185	Remote Similarity	NPC488217
0.5185	Remote Similarity	NPC488218
0.5125	Remote Similarity	NPC473399
0.5125	Remote Similarity	NPC473216
0.5065	Remote Similarity	NPC127933
0.5062	Remote Similarity	NPC162569
0.5062	Remote Similarity	NPC35160

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC318917 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7090
0.1-0.2	2044
0.2-0.3	16
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