NPASS Compound

Structure

CID323677 OpenBabel06191716172D 22 22 0 0 1 0 0 0 0 0999 V2000 -1.9783 2.7568 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6499 -2.0226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0544 2.3741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7071 1.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4142 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2672 -1.0987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9239 1.3827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7071 1.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2758 -0.9682 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4142 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2587 -1.2292 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3244 -1.6310 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0411 -2.8159 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6670 -1.7615 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7071 -0.7071 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7071 -0.7071 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6414 -2.1531 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 2.0898 -1.6310 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -2.4238 -3.7398 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0497 -2.6854 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 1 0 0 0 0 2 13 1 0 0 0 0 3 7 2 0 0 0 0 4 5 2 0 0 0 0 4 8 1 0 0 0 0 5 10 1 0 0 0 0 6 9 2 0 0 0 0 6 11 2 0 0 0 0 8 14 1 0 0 0 0 10 16 1 0 0 0 0 11 18 1 0 0 0 0 12 15 1 0 0 0 0 13 20 2 0 0 0 0 13 21 1 0 0 0 0 14 7 1 1 0 0 0 14 22 1 0 0 0 0 15 9 1 1 0 0 0 15 21 1 0 0 0 0 16 17 1 0 0 0 0 16 19 1 1 0 0 0 17 12 1 1 0 0 0 17 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	388.04
Volume:	341.715
LogP:	4.528
LogD:	3.048
LogS:	-4.231
# Rotatable Bonds:	6
TPSA:	35.53
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.297
Synthetic Accessibility Score:	5.124
Fsp3:	0.529
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.63
MDCK Permeability:	9.789721843844745e-06
Pgp-inhibitor:	0.923
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.019
20% Bioavailability (F20%):	0.008
30% Bioavailability (F30%):	0.63

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.493
Plasma Protein Binding (PPB):	98.38199615478516%
Volume Distribution (VD):	1.653
Pgp-substrate:	2.4349730014801025%

ADMET: Metabolism

CYP1A2-inhibitor:	0.03
CYP1A2-substrate:	0.083
CYP2C19-inhibitor:	0.028
CYP2C19-substrate:	0.68
CYP2C9-inhibitor:	0.018
CYP2C9-substrate:	0.218
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.116
CYP3A4-inhibitor:	0.272
CYP3A4-substrate:	0.227

ADMET: Excretion

Clearance (CL):	1.998
Half-life (T1/2):	0.502

ADMET: Toxicity

hERG Blockers:	0.299
Human Hepatotoxicity (H-HT):	0.918
Drug-inuced Liver Injury (DILI):	0.879
AMES Toxicity:	0.981
Rat Oral Acute Toxicity:	0.05
Maximum Recommended Daily Dose:	0.951
Skin Sensitization:	0.977
Carcinogencity:	0.348
Eye Corrosion:	0.088
Eye Irritation:	0.302
Respiratory Toxicity:	0.895

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC323677

Natural Product ID:	NPC323677
*Common Name:**	(+)-4-Acetoxymarilzallene
IUPAC Name:	[(2R)-5-bromo-1-[(2R,3R,5Z,8R)-3-chloro-8-[(E)-prop-1-enyl]-3,4,7,8-tetrahydro-2H-oxocin-2-yl]penta-3,4-dien-2-yl] acetate
Synonyms:	(+)-4-Acetoxymarilzallene
Standard InCHIKey:	BUAQGGUCIOVTOG-RWVYZSKESA-N
Standard InCHI:	InChI=1S/C17H22BrClO3/c1-3-7-14-8-4-5-10-16(19)17(22-14)12-15(9-6-11-18)21-13(2)20/h3-5,7,9,11,14-17H,8,10,12H2,1-2H3/b5-4-,7-3+/t6?,14-,15-,16+,17+/m0/s1
SMILES:	CC=CC1CC=CCC(C(O1)CC(C=C=CBr)OC(=O)C)Cl
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1765723
PubChem CID:	52936651
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001796] Oxocins

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO30005	Laurencia marilzae	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21338119]
NPO30005	Laurencia marilzae	Species	Rhodomelaceae	Eukaryota	n.a.	Paraso Floral, Tenerife, Canary Islands	n.a.	PMID[21338119]

☑ 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	NP ID	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
GI50	6

Activity Type	# Activity
Cell Line	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell Line	A2780	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[482931]
NPT1723	Cell Line	HBL-100	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[482931]
NPT165	Cell Line	HeLa	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[482931]
NPT1577	Cell Line	SW1573	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[482931]
NPT396	Cell Line	T47D	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[482931]
NPT1183	Cell Line	WiDr	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[482931]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC323677 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	205
0.1-0.2	4202
0.2-0.3	20344
0.3-0.4	12725
0.4-0.5	4203
0.5-0.6	918
0.6-0.7	89
0.7-0.8	8
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC477429
0.8429	Intermediate Similarity	NPC316572
0.7867	Intermediate Similarity	NPC477421
0.7778	Intermediate Similarity	NPC477431
0.7568	Intermediate Similarity	NPC477423
0.75	Intermediate Similarity	NPC77724
0.747	Intermediate Similarity	NPC477428
0.7353	Intermediate Similarity	NPC26310
0.7286	Intermediate Similarity	NPC477424
0.7037	Intermediate Similarity	NPC473947
0.6901	Remote Similarity	NPC474267
0.6901	Remote Similarity	NPC22897
0.6901	Remote Similarity	NPC159650
0.675	Remote Similarity	NPC52781
0.6667	Remote Similarity	NPC478095
0.6627	Remote Similarity	NPC477088
0.6625	Remote Similarity	NPC477422
0.6623	Remote Similarity	NPC475760
0.6582	Remote Similarity	NPC473306
0.6575	Remote Similarity	NPC26223
0.6533	Remote Similarity	NPC148233
0.6533	Remote Similarity	NPC25747
0.6533	Remote Similarity	NPC308457
0.6528	Remote Similarity	NPC478096
0.6456	Remote Similarity	NPC476012
0.6456	Remote Similarity	NPC476037
0.6438	Remote Similarity	NPC222852
0.6418	Remote Similarity	NPC207815
0.64	Remote Similarity	NPC217940
0.6389	Remote Similarity	NPC471277
0.6389	Remote Similarity	NPC471279
0.6389	Remote Similarity	NPC212730
0.6389	Remote Similarity	NPC265551
0.6377	Remote Similarity	NPC106531
0.6375	Remote Similarity	NPC475762
0.6364	Remote Similarity	NPC248125
0.6364	Remote Similarity	NPC146811
0.6364	Remote Similarity	NPC284447
0.6364	Remote Similarity	NPC124586
0.6351	Remote Similarity	NPC299730
0.6338	Remote Similarity	NPC474913
0.6296	Remote Similarity	NPC329890
0.6296	Remote Similarity	NPC327383
0.6296	Remote Similarity	NPC329914
0.6296	Remote Similarity	NPC185186
0.6267	Remote Similarity	NPC325929
0.6267	Remote Similarity	NPC113293
0.6267	Remote Similarity	NPC26810
0.6267	Remote Similarity	NPC271282
0.6267	Remote Similarity	NPC66460
0.625	Remote Similarity	NPC325098
0.625	Remote Similarity	NPC30915
0.6234	Remote Similarity	NPC182794
0.6216	Remote Similarity	NPC286189
0.6203	Remote Similarity	NPC474823
0.6203	Remote Similarity	NPC218477
0.6197	Remote Similarity	NPC269615
0.6197	Remote Similarity	NPC137538
0.6184	Remote Similarity	NPC179087
0.6184	Remote Similarity	NPC29697
0.6184	Remote Similarity	NPC210303
0.6184	Remote Similarity	NPC44343
0.6164	Remote Similarity	NPC44542
0.6163	Remote Similarity	NPC121374
0.6145	Remote Similarity	NPC285840
0.6145	Remote Similarity	NPC327041
0.6133	Remote Similarity	NPC477430
0.6133	Remote Similarity	NPC471278
0.6133	Remote Similarity	NPC19241
0.6125	Remote Similarity	NPC151481
0.6125	Remote Similarity	NPC101622
0.6125	Remote Similarity	NPC475004
0.6119	Remote Similarity	NPC197467
0.6111	Remote Similarity	NPC52264
0.6111	Remote Similarity	NPC474672
0.6104	Remote Similarity	NPC477456
0.6104	Remote Similarity	NPC477457
0.6081	Remote Similarity	NPC23418
0.6076	Remote Similarity	NPC25298
0.6076	Remote Similarity	NPC478097
0.6076	Remote Similarity	NPC478100
0.6076	Remote Similarity	NPC194871
0.6076	Remote Similarity	NPC472266
0.6071	Remote Similarity	NPC188860
0.6067	Remote Similarity	NPC475732
0.6053	Remote Similarity	NPC320305
0.6053	Remote Similarity	NPC55376
0.6053	Remote Similarity	NPC151648
0.6053	Remote Similarity	NPC328776
0.6049	Remote Similarity	NPC4299
0.6049	Remote Similarity	NPC469660
0.6047	Remote Similarity	NPC199134
0.6047	Remote Similarity	NPC286816
0.6027	Remote Similarity	NPC327388
0.6027	Remote Similarity	NPC245002
0.6026	Remote Similarity	NPC96414
0.6026	Remote Similarity	NPC478098
0.6026	Remote Similarity	NPC19769
0.6026	Remote Similarity	NPC282760
0.6026	Remote Similarity	NPC478099
0.6024	Remote Similarity	NPC92558
0.6	Remote Similarity	NPC474026
0.6	Remote Similarity	NPC276290
0.6	Remote Similarity	NPC48210
0.6	Remote Similarity	NPC57923
0.6	Remote Similarity	NPC469570
0.6	Remote Similarity	NPC233071
0.6	Remote Similarity	NPC470256
0.5976	Remote Similarity	NPC293114
0.5976	Remote Similarity	NPC477087
0.5976	Remote Similarity	NPC477086
0.5976	Remote Similarity	NPC477084
0.5976	Remote Similarity	NPC316185
0.5976	Remote Similarity	NPC472254
0.5976	Remote Similarity	NPC163003
0.5974	Remote Similarity	NPC54925
0.5974	Remote Similarity	NPC474774
0.597	Remote Similarity	NPC26600
0.597	Remote Similarity	NPC47946
0.5952	Remote Similarity	NPC260396
0.5949	Remote Similarity	NPC478101
0.5949	Remote Similarity	NPC276299
0.5949	Remote Similarity	NPC201356
0.5946	Remote Similarity	NPC323597
0.5946	Remote Similarity	NPC211752
0.5946	Remote Similarity	NPC323498
0.5942	Remote Similarity	NPC135698
0.5942	Remote Similarity	NPC163345
0.5934	Remote Similarity	NPC184461
0.593	Remote Similarity	NPC28049
0.593	Remote Similarity	NPC248775
0.5926	Remote Similarity	NPC269841
0.5926	Remote Similarity	NPC130618
0.5926	Remote Similarity	NPC470436
0.5921	Remote Similarity	NPC252851
0.5921	Remote Similarity	NPC226872
0.5921	Remote Similarity	NPC158368
0.5921	Remote Similarity	NPC328311
0.5921	Remote Similarity	NPC154908
0.5921	Remote Similarity	NPC327112
0.5904	Remote Similarity	NPC284006
0.5904	Remote Similarity	NPC16349
0.5904	Remote Similarity	NPC477085
0.5904	Remote Similarity	NPC474705
0.5904	Remote Similarity	NPC470435
0.5904	Remote Similarity	NPC222244
0.5897	Remote Similarity	NPC471460
0.5897	Remote Similarity	NPC34883
0.5897	Remote Similarity	NPC68343
0.5897	Remote Similarity	NPC328089
0.589	Remote Similarity	NPC128061
0.589	Remote Similarity	NPC10316
0.589	Remote Similarity	NPC223677
0.589	Remote Similarity	NPC200845
0.589	Remote Similarity	NPC28779
0.5889	Remote Similarity	NPC282598
0.5882	Remote Similarity	NPC301525
0.5875	Remote Similarity	NPC225272
0.5875	Remote Similarity	NPC122627
0.5875	Remote Similarity	NPC203335
0.587	Remote Similarity	NPC475405
0.5862	Remote Similarity	NPC470149
0.5862	Remote Similarity	NPC470148
0.5862	Remote Similarity	NPC471537
0.5862	Remote Similarity	NPC139712
0.5862	Remote Similarity	NPC180725
0.5862	Remote Similarity	NPC1180
0.5857	Remote Similarity	NPC275316
0.5854	Remote Similarity	NPC329904
0.5854	Remote Similarity	NPC473361
0.5844	Remote Similarity	NPC201939
0.5833	Remote Similarity	NPC474280
0.5833	Remote Similarity	NPC476355
0.5833	Remote Similarity	NPC474758
0.5833	Remote Similarity	NPC315843
0.5833	Remote Similarity	NPC477204
0.5833	Remote Similarity	NPC71761
0.5833	Remote Similarity	NPC140287
0.5833	Remote Similarity	NPC107654
0.5814	Remote Similarity	NPC474278
0.5814	Remote Similarity	NPC97516
0.5814	Remote Similarity	NPC476028
0.5814	Remote Similarity	NPC141789
0.5814	Remote Similarity	NPC171204
0.5811	Remote Similarity	NPC96663
0.5811	Remote Similarity	NPC86948
0.5806	Remote Similarity	NPC475712
0.5802	Remote Similarity	NPC63873
0.5802	Remote Similarity	NPC310210
0.5802	Remote Similarity	NPC238223
0.5795	Remote Similarity	NPC133226
0.5795	Remote Similarity	NPC470147
0.5789	Remote Similarity	NPC329249
0.5789	Remote Similarity	NPC97570
0.5783	Remote Similarity	NPC162571
0.5783	Remote Similarity	NPC112983
0.5783	Remote Similarity	NPC84038
0.5783	Remote Similarity	NPC186531
0.5765	Remote Similarity	NPC329826
0.5765	Remote Similarity	NPC469414

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC323677 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	194
0.1-0.2	3862
0.2-0.3	3994
0.3-0.4	967
0.4-0.5	107
0.5-0.6	26
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
0.6234	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6	Remote Similarity	NPD6927	Phase 3
0.5921	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.5876	Remote Similarity	NPD4792	Clinical (unspecified phase)
0.5797	Remote Similarity	NPD5343	Approved

Bioactivity similarity: Similar Natural Products in NPASS

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