NPASS Compound

Structure

NPC198644 OpenBabel07101718282D 54 58 0 0 1 0 0 0 0 0999 V2000 -7.6742 -2.8472 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3759 -0.9325 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7191 -1.8482 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8764 -1.3098 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9888 -1.7705 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1461 -1.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4464 0.7437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3124 0.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5804 0.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2585 -1.6928 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1784 0.7437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7143 0.7437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4157 -1.1544 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0445 0.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3124 -2.7563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8483 0.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1784 -2.2563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.8450 -2.3389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5282 -1.6151 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9105 0.7437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.8505 -2.2344 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7238 1.4471 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2651 1.5962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3124 -3.7563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.2517 -1.4254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9823 0.7437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1784 -1.2563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7303 -0.0777 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4450 -0.5671 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6854 -1.0767 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8876 0.4606 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 11.7765 0.2437 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 12.6425 -1.2563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7124 0.7018 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3842 0.2437 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 11.7765 -0.7563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2502 0.7437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9105 -1.2563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1784 -5.2563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.5086 0.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0449 -0.9990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3124 -5.7563 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 10.0445 -5.7563 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 14.3746 0.7437 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 9.1784 -4.2563 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.8489 -1.1202 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.7979 -1.5373 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 12.6425 0.7437 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 13.5086 -0.7563 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.2502 1.7437 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.9105 -2.2563 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1163 0.2437 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.0445 -0.7563 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 6 10 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 8 11 1 0 0 0 0 9 12 1 0 0 0 0 10 13 1 0 0 0 0 11 14 1 0 0 0 0 12 16 1 0 0 0 0 13 19 1 0 0 0 0 14 20 1 0 0 0 0 15 17 1 0 0 0 0 15 24 1 0 0 0 0 16 26 1 0 0 0 0 17 27 1 0 0 0 0 18 21 1 0 0 0 0 18 25 1 0 0 0 0 21 33 1 0 0 0 0 22 23 1 0 0 0 0 24 45 1 0 0 0 0 25 49 1 0 0 0 0 26 53 1 0 0 0 0 27 54 1 0 0 0 0 28 30 1 0 0 0 0 28 31 1 0 0 0 0 29 2 1 1 0 0 0 29 35 1 0 0 0 0 29 46 1 0 0 0 0 30 19 1 6 0 0 0 30 47 1 0 0 0 0 31 22 1 6 0 0 0 31 50 1 0 0 0 0 32 20 1 1 0 0 0 32 36 1 0 0 0 0 32 48 1 0 0 0 0 33 36 2 0 0 0 0 33 49 1 0 0 0 0 34 23 1 1 0 0 0 34 35 1 0 0 0 0 34 50 1 0 0 0 0 35 37 1 1 0 0 0 36 38 1 0 0 0 0 37 51 2 0 0 0 0 37 53 1 0 0 0 0 38 52 2 0 0 0 0 38 54 1 0 0 0 0 39 42 2 0 0 0 0 39 43 1 0 0 0 0 39 45 1 0 0 0 0 40 44 2 0 0 0 0 40 48 1 0 0 0 0 40 49 1 0 0 0 0 41 46 2 0 0 0 0 41 47 1 0 0 0 0 41 50 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	753.56
Volume:	793.223
LogP:	6.685
LogD:	3.527
LogS:	-6.521
# Rotatable Bonds:	26
TPSA:	186.25
# H-Bond Aceptor:	13
# H-Bond Donor:	7
# Rings:	5
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.043
Synthetic Accessibility Score:	5.4
Fsp3:	0.829
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.312
MDCK Permeability:	5.727311145165004e-05
Pgp-inhibitor:	0.008
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.013
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.574
Plasma Protein Binding (PPB):	81.49723052978516%
Volume Distribution (VD):	0.758
Pgp-substrate:	22.744604110717773%

ADMET: Metabolism

CYP1A2-inhibitor:	0.01
CYP1A2-substrate:	0.077
CYP2C19-inhibitor:	0.038
CYP2C19-substrate:	0.038
CYP2C9-inhibitor:	0.024
CYP2C9-substrate:	0.012
CYP2D6-inhibitor:	0.956
CYP2D6-substrate:	0.189
CYP3A4-inhibitor:	0.952
CYP3A4-substrate:	0.294

ADMET: Excretion

Clearance (CL):	4.589
Half-life (T1/2):	0.011

ADMET: Toxicity

hERG Blockers:	0.709
Human Hepatotoxicity (H-HT):	0.988
Drug-inuced Liver Injury (DILI):	0.499
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.465
Maximum Recommended Daily Dose:	0.949
Skin Sensitization:	0.945
Carcinogencity:	0.024
Eye Corrosion:	0.003
Eye Irritation:	0.003
Respiratory Toxicity:	0.847

Download Data

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

Natural Product: NPC198644

Natural Product ID:	NPC198644
*Common Name:**	Norbatzelladine A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	DPZMUSXOHQXFRG-IEIJWRJASA-N
Standard InCHI:	InChI=1S/C41H71N9O4/c1-3-4-5-6-10-13-19-30-28-31-22-23-34-35(29(2)46-41(47-30)50(31)34)37(51)53-26-16-12-9-7-8-11-14-20-32-36(33-21-18-25-49(33)40(44)48-32)38(52)54-27-17-15-24-45-39(42)43/h29-32,34-35H,3-28H2,1-2H3,(H2,44,48)(H,46,47)(H4,42,43,45)/t29-,30-,31+,32-,34+,35+/m1/s1
SMILES:	CCCCCCCC[C@@H]1C[C@@H]2CC[C@@H]3N2C(=N[C@@H]([C@@H]3C(=O)OCCCCCCCCC[C@H]2NC(=N)N3C(=C2C(=O)OCCCCNC(=N)N)CCC3)C)N1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1077519
PubChem CID:	44480474
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001346] Diazines [CHEMONTID:0000075] Pyrimidines and pyrimidine derivatives [CHEMONTID:0002202] Hydropyrimidines

*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
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[19743809]
NPO33489	clathria calla	Species	Microcionidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[19743809]
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	n.a.	n.a.	PMID[25924111]
NPO8412	Monanchora arbuscula	Species	Crambeidae	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	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	3
IC50	1
Others	8

Activity Type	# Activity
Cell Line	10
Organism	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	1600.0	nM	PMID[527435]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	2100.0	nM	PMID[527435]
NPT139	Cell Line	HT-29	Homo sapiens	TGI	=	3200.0	nM	PMID[527435]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	=	3800.0	nM	PMID[527435]
NPT81	Cell Line	A549	Homo sapiens	TGI	=	4600.0	nM	PMID[527435]
NPT165	Cell Line	HeLa	Homo sapiens	TC50	=	4.7	uM	PMID[527435]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	=	5700.0	nM	PMID[527435]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	TGI	=	6400.0	nM	PMID[527435]
NPT81	Cell Line	A549	Homo sapiens	LC50	=	8600.0	nM	PMID[527435]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	LC50	=	11400.0	nM	PMID[527435]
NPT1225	Organism	Plasmodium falciparum (isolate FcB1 / Columbia)	Plasmodium falciparum FcB1/Columbia	IC50	=	200.0	nM	PMID[527435]
NPT2	Others	Unspecified		Selectivity Index	=	23.5	n.a.	PMID[527435]

☑ 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 NPC198644 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	132
0.1-0.2	1080
0.2-0.3	15548
0.3-0.4	19167
0.4-0.5	6386
0.5-0.6	331
0.6-0.7	25
0.7-0.8	16
0.8-0.85	8
0.85-0.9	0
0.9-0.95	1
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC311244
1.0	High Similarity	NPC324722
0.8583	High Similarity	NPC469387
0.813	Intermediate Similarity	NPC469423
0.7724	Intermediate Similarity	NPC469389
0.7724	Intermediate Similarity	NPC472737
0.7724	Intermediate Similarity	NPC469388
0.7627	Intermediate Similarity	NPC472736
0.7561	Intermediate Similarity	NPC467022
0.7246	Intermediate Similarity	NPC261730
0.7192	Intermediate Similarity	NPC477519
0.7172	Intermediate Similarity	NPC142761
0.6795	Remote Similarity	NPC322372
0.6795	Remote Similarity	NPC319334
0.6795	Remote Similarity	NPC327517
0.6582	Remote Similarity	NPC317377
0.6582	Remote Similarity	NPC321485
0.6454	Remote Similarity	NPC477518
0.6331	Remote Similarity	NPC471261
0.6299	Remote Similarity	NPC476449
0.6299	Remote Similarity	NPC3604
0.6296	Remote Similarity	NPC147238
0.622	Remote Similarity	NPC469424
0.6212	Remote Similarity	NPC87919
0.6067	Remote Similarity	NPC471256
0.6047	Remote Similarity	NPC471257
0.6045	Remote Similarity	NPC471259
0.6015	Remote Similarity	NPC471260
0.6013	Remote Similarity	NPC473955
0.5986	Remote Similarity	NPC478136
0.597	Remote Similarity	NPC133420
0.5959	Remote Similarity	NPC471263
0.594	Remote Similarity	NPC471258
0.5931	Remote Similarity	NPC471255
0.5862	Remote Similarity	NPC471262
0.5846	Remote Similarity	NPC150041
0.5845	Remote Similarity	NPC477121
0.5827	Remote Similarity	NPC304455
0.5827	Remote Similarity	NPC58281
0.5766	Remote Similarity	NPC271562
0.5758	Remote Similarity	NPC476344
0.5758	Remote Similarity	NPC472162
0.5758	Remote Similarity	NPC241426
0.5725	Remote Similarity	NPC470382
0.5725	Remote Similarity	NPC25033
0.5725	Remote Similarity	NPC119225
0.5725	Remote Similarity	NPC471635
0.5725	Remote Similarity	NPC476261
0.5724	Remote Similarity	NPC139867
0.5705	Remote Similarity	NPC473249
0.5705	Remote Similarity	NPC317654
0.5705	Remote Similarity	NPC96010
0.5695	Remote Similarity	NPC478139
0.5686	Remote Similarity	NPC475987
0.5686	Remote Similarity	NPC313348
0.5685	Remote Similarity	NPC245534
0.5669	Remote Similarity	NPC304454
0.5658	Remote Similarity	NPC120335
0.562	Remote Similarity	NPC477000
0.562	Remote Similarity	NPC477001
0.5616	Remote Similarity	NPC11379
0.5603	Remote Similarity	NPC79238

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 NPC198644 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	99
0.1-0.2	335
0.2-0.3	2378
0.3-0.4	5298
0.4-0.5	985
0.5-0.6	55
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
0.5793	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5743	Remote Similarity	NPD4816	Clinical (unspecified phase)
0.5742	Remote Similarity	NPD5767	Discontinued
0.5734	Remote Similarity	NPD961	Discontinued
0.5724	Remote Similarity	NPD1689	Approved
0.5705	Remote Similarity	NPD7747	Phase 1
0.5705	Remote Similarity	NPD7746	Phase 1
0.5682	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.5673	Remote Similarity	NPD7591	Clinical (unspecified phase)
0.5646	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.5646	Remote Similarity	NPD7623	Phase 3

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