NPASS Compound

Structure

NPC94127 OpenBabel07101718282D 31 34 0 0 1 0 0 0 0 0999 V2000 -4.1905 1.3625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3877 -1.4942 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3989 -1.3452 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5053 1.5890 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8545 1.6774 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8433 1.5283 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7504 -0.9037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5931 -0.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1214 0.9972 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.9780 -0.2686 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.3433 0.6623 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 1 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 -6.0224 -0.5633 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.3415 0.6025 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.2778 0.9539 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0981 -2.3660 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 17 1 0 0 0 0 2 24 1 0 0 0 0 3 24 1 0 0 0 0 7 8 1 0 0 0 0 7 17 2 0 0 0 0 8 20 1 0 0 0 0 9 10 1 0 0 0 0 10 21 1 0 0 0 0 11 15 1 0 0 0 0 12 16 1 0 0 0 0 12 22 1 0 0 0 0 13 14 1 0 0 0 0 13 23 1 0 0 0 0 14 25 1 0 0 0 0 15 26 1 0 0 0 0 16 27 1 0 0 0 0 17 18 1 0 0 0 0 18 9 1 1 0 0 0 18 24 1 0 0 0 0 19 11 1 1 0 0 0 19 20 1 0 0 0 0 19 24 1 0 0 0 0 20 26 1 1 0 0 0 21 25 1 1 0 0 0 21 27 1 0 0 0 0 22 25 1 1 0 0 0 22 31 1 0 0 0 0 23 28 1 1 0 0 0 23 31 1 0 0 0 0 25 4 1 1 0 0 0 26 5 1 1 0 0 0 26 29 1 0 0 0 0 27 6 1 6 0 0 0 27 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	434.34
Volume:	473.847
LogP:	5.854
LogD:	4.248
LogS:	-4.44
# Rotatable Bonds:	3
TPSA:	69.92
# H-Bond Aceptor:	4
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.534
Synthetic Accessibility Score:	5.21
Fsp3:	0.926
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.569
MDCK Permeability:	1.640835398575291e-05
Pgp-inhibitor:	0.993
Pgp-substrate:	0.731
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.466
30% Bioavailability (F30%):	0.013

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.407
Plasma Protein Binding (PPB):	89.94141387939453%
Volume Distribution (VD):	1.627
Pgp-substrate:	7.190827369689941%

ADMET: Metabolism

CYP1A2-inhibitor:	0.013
CYP1A2-substrate:	0.331
CYP2C19-inhibitor:	0.031
CYP2C19-substrate:	0.831
CYP2C9-inhibitor:	0.137
CYP2C9-substrate:	0.034
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.107
CYP3A4-inhibitor:	0.657
CYP3A4-substrate:	0.378

ADMET: Excretion

Clearance (CL):	13.067
Half-life (T1/2):	0.049

ADMET: Toxicity

hERG Blockers:	0.25
Human Hepatotoxicity (H-HT):	0.376
Drug-inuced Liver Injury (DILI):	0.023
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.912
Maximum Recommended Daily Dose:	0.933
Skin Sensitization:	0.923
Carcinogencity:	0.743
Eye Corrosion:	0.68
Eye Irritation:	0.052
Respiratory Toxicity:	0.957

Download Data

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

Natural Product: NPC94127

Natural Product ID:	NPC94127
*Common Name:**	(2S,4As,5S,6R)-5-(2-((1S,3As,5R,8As)-1-Hydroxy-1,4,4,6-Tetramethyl-1,2,3,3A,4,5,8,8A-Octahydroazulen-5-Yl)Ethyl)-4A,6-Dimethyloctahydro-2H-Chromene-2,6-Diol
IUPAC Name:	(2S,4aS,5S,6R,8aS)-5-[2-[(1S,3aS,5R,8aS)-1-hydroxy-1,4,4,6-tetramethyl-2,3,3a,5,8,8a-hexahydroazulen-5-yl]ethyl]-4a,6-dimethyl-3,4,5,7,8,8a-hexahydro-2H-chromene-2,6-diol
Synonyms:
Standard InCHIKey:	QHUWGQUBUQPIRE-DEOUKZKDSA-N
Standard InCHI:	InChI=1S/C27H46O4/c1-17-7-8-20-19(11-15-26(20,5)29)24(2,3)18(17)9-10-21-25(4)14-13-23(28)31-22(25)12-16-27(21,6)30/h7,18-23,28-30H,8-16H2,1-6H3/t18-,19+,20+,21+,22+,23+,25+,26+,27-/m1/s1
SMILES:	CC1=CC[C@H]2[C@H](CC[C@]2(C)O)C(C)(C)[C@@H]1CC[C@H]1[C@]2(C)CC[C@@H](O)O[C@H]2CC[C@@]1(C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL550866
PubChem CID:	44234694
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans

*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
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17488128]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19534474]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	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
IC50	4
Others	2

Activity Type	# Activity
Cell Line	4
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	>	50000.0	nM	PMID[533881]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	>	50000.0	nM	PMID[533881]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	48000.0	nM	PMID[533881]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	47973.34	nM	PMID[533881]
NPT668	Individual Protein	P-glycoprotein 1	Homo sapiens	Ratio IC50	=	1.0	n.a.	PMID[533880]
NPT668	Individual Protein	P-glycoprotein 1	Homo sapiens	Ratio IC50	=	70.0	n.a.	PMID[533880]

☑ 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 NPC94127 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	184
0.1-0.2	1601
0.2-0.3	6196
0.3-0.4	15361
0.4-0.5	7506
0.5-0.6	5483
0.6-0.7	5003
0.7-0.8	1338
0.8-0.85	24
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8571	High Similarity	NPC470832
0.8298	Intermediate Similarity	NPC473258
0.8222	Intermediate Similarity	NPC308041
0.8222	Intermediate Similarity	NPC16350
0.8202	Intermediate Similarity	NPC110778
0.8163	Intermediate Similarity	NPC129372
0.8163	Intermediate Similarity	NPC88000
0.8163	Intermediate Similarity	NPC474022
0.8163	Intermediate Similarity	NPC4831
0.8163	Intermediate Similarity	NPC472023
0.8163	Intermediate Similarity	NPC160734
0.8163	Intermediate Similarity	NPC309425
0.8163	Intermediate Similarity	NPC47566
0.8144	Intermediate Similarity	NPC216260
0.8144	Intermediate Similarity	NPC234287
0.8144	Intermediate Similarity	NPC5358
0.8144	Intermediate Similarity	NPC280825
0.8132	Intermediate Similarity	NPC201273
0.8111	Intermediate Similarity	NPC124172
0.8081	Intermediate Similarity	NPC136816
0.8061	Intermediate Similarity	NPC324598
0.8061	Intermediate Similarity	NPC473200
0.8061	Intermediate Similarity	NPC7341
0.8041	Intermediate Similarity	NPC476893
0.8041	Intermediate Similarity	NPC177818
0.8021	Intermediate Similarity	NPC476894
0.802	Intermediate Similarity	NPC26798
0.802	Intermediate Similarity	NPC242748
0.8	Intermediate Similarity	NPC211879
0.8	Intermediate Similarity	NPC114874
0.8	Intermediate Similarity	NPC120123
0.8	Intermediate Similarity	NPC189852
0.8	Intermediate Similarity	NPC472252
0.8	Intermediate Similarity	NPC242419
0.8	Intermediate Similarity	NPC155010
0.8	Intermediate Similarity	NPC213190
0.8	Intermediate Similarity	NPC475701
0.8	Intermediate Similarity	NPC31907
0.8	Intermediate Similarity	NPC245280
0.8	Intermediate Similarity	NPC286969
0.8	Intermediate Similarity	NPC477818
0.8	Intermediate Similarity	NPC193870
0.8	Intermediate Similarity	NPC131479
0.8	Intermediate Similarity	NPC473020
0.8	Intermediate Similarity	NPC141941
0.8	Intermediate Similarity	NPC8039
0.8	Intermediate Similarity	NPC235126
0.8	Intermediate Similarity	NPC16520
0.8	Intermediate Similarity	NPC157659
0.7959	Intermediate Similarity	NPC476895
0.7941	Intermediate Similarity	NPC226642
0.7941	Intermediate Similarity	NPC473469
0.7935	Intermediate Similarity	NPC6605
0.7935	Intermediate Similarity	NPC24277
0.7921	Intermediate Similarity	NPC273879
0.7921	Intermediate Similarity	NPC187400
0.7921	Intermediate Similarity	NPC470885
0.7921	Intermediate Similarity	NPC221562
0.7921	Intermediate Similarity	NPC165033
0.7921	Intermediate Similarity	NPC474464
0.7921	Intermediate Similarity	NPC312774
0.7921	Intermediate Similarity	NPC475365
0.7912	Intermediate Similarity	NPC127606
0.7912	Intermediate Similarity	NPC475798
0.79	Intermediate Similarity	NPC159036
0.79	Intermediate Similarity	NPC288694
0.79	Intermediate Similarity	NPC312553
0.79	Intermediate Similarity	NPC22634
0.7895	Intermediate Similarity	NPC210268
0.7889	Intermediate Similarity	NPC470614
0.7889	Intermediate Similarity	NPC1272
0.7865	Intermediate Similarity	NPC102253
0.7865	Intermediate Similarity	NPC236237
0.7865	Intermediate Similarity	NPC322313
0.7864	Intermediate Similarity	NPC7213
0.7857	Intermediate Similarity	NPC473890
0.7857	Intermediate Similarity	NPC243728
0.7857	Intermediate Similarity	NPC76486
0.7843	Intermediate Similarity	NPC472899
0.7843	Intermediate Similarity	NPC474569
0.7843	Intermediate Similarity	NPC208594
0.7843	Intermediate Similarity	NPC269627
0.7843	Intermediate Similarity	NPC473476
0.7843	Intermediate Similarity	NPC69737
0.7843	Intermediate Similarity	NPC194842
0.7843	Intermediate Similarity	NPC474015
0.7843	Intermediate Similarity	NPC473923
0.7843	Intermediate Similarity	NPC152584
0.7843	Intermediate Similarity	NPC472898
0.7843	Intermediate Similarity	NPC473199
0.7843	Intermediate Similarity	NPC160816
0.7843	Intermediate Similarity	NPC127801
0.7843	Intermediate Similarity	NPC208477
0.7843	Intermediate Similarity	NPC472900
0.7826	Intermediate Similarity	NPC290731
0.7822	Intermediate Similarity	NPC471887
0.7822	Intermediate Similarity	NPC471888
0.7822	Intermediate Similarity	NPC471885
0.7822	Intermediate Similarity	NPC473198
0.7822	Intermediate Similarity	NPC471886
0.7822	Intermediate Similarity	NPC16573
0.7812	Intermediate Similarity	NPC98193
0.781	Intermediate Similarity	NPC197231
0.78	Intermediate Similarity	NPC176406
0.78	Intermediate Similarity	NPC476896
0.7788	Intermediate Similarity	NPC476835
0.7778	Intermediate Similarity	NPC309493
0.7778	Intermediate Similarity	NPC158088
0.7778	Intermediate Similarity	NPC275865
0.7767	Intermediate Similarity	NPC63368
0.7767	Intermediate Similarity	NPC231340
0.7767	Intermediate Similarity	NPC208650
0.7767	Intermediate Similarity	NPC190395
0.7767	Intermediate Similarity	NPC181467
0.7767	Intermediate Similarity	NPC14946
0.7766	Intermediate Similarity	NPC470542
0.7755	Intermediate Similarity	NPC90583
0.7755	Intermediate Similarity	NPC304899
0.7755	Intermediate Similarity	NPC207617
0.7755	Intermediate Similarity	NPC253115
0.7755	Intermediate Similarity	NPC472989
0.7753	Intermediate Similarity	NPC273410
0.7753	Intermediate Similarity	NPC80530
0.7753	Intermediate Similarity	NPC1319
0.7745	Intermediate Similarity	NPC85593
0.7745	Intermediate Similarity	NPC75608
0.7745	Intermediate Similarity	NPC31430
0.7745	Intermediate Similarity	NPC471111
0.7742	Intermediate Similarity	NPC139724
0.7736	Intermediate Similarity	NPC19888
0.7736	Intermediate Similarity	NPC216595
0.7736	Intermediate Similarity	NPC473567
0.7732	Intermediate Similarity	NPC305160
0.7732	Intermediate Similarity	NPC477927
0.7732	Intermediate Similarity	NPC72817
0.7723	Intermediate Similarity	NPC471889
0.7723	Intermediate Similarity	NPC37207
0.7723	Intermediate Similarity	NPC300399
0.7723	Intermediate Similarity	NPC471482
0.7717	Intermediate Similarity	NPC209802
0.77	Intermediate Similarity	NPC282669
0.77	Intermediate Similarity	NPC324841
0.77	Intermediate Similarity	NPC91497
0.77	Intermediate Similarity	NPC471242
0.7692	Intermediate Similarity	NPC472988
0.7692	Intermediate Similarity	NPC38217
0.7692	Intermediate Similarity	NPC6931
0.7692	Intermediate Similarity	NPC476538
0.7692	Intermediate Similarity	NPC180183
0.7692	Intermediate Similarity	NPC159005
0.7692	Intermediate Similarity	NPC122945
0.7692	Intermediate Similarity	NPC246124
0.7692	Intermediate Similarity	NPC476539
0.7692	Intermediate Similarity	NPC220427
0.7692	Intermediate Similarity	NPC476540
0.7692	Intermediate Similarity	NPC476541
0.7692	Intermediate Similarity	NPC109938
0.7684	Intermediate Similarity	NPC109744
0.7684	Intermediate Similarity	NPC470819
0.7684	Intermediate Similarity	NPC105495
0.7677	Intermediate Similarity	NPC475033
0.7677	Intermediate Similarity	NPC475032
0.7677	Intermediate Similarity	NPC26307
0.767	Intermediate Similarity	NPC309448
0.767	Intermediate Similarity	NPC181845
0.7667	Intermediate Similarity	NPC78545
0.7667	Intermediate Similarity	NPC71535
0.7667	Intermediate Similarity	NPC206062
0.7667	Intermediate Similarity	NPC26117
0.7664	Intermediate Similarity	NPC476693
0.766	Intermediate Similarity	NPC474657
0.766	Intermediate Similarity	NPC189777
0.766	Intermediate Similarity	NPC271967
0.766	Intermediate Similarity	NPC186145
0.7653	Intermediate Similarity	NPC477969
0.7653	Intermediate Similarity	NPC135224
0.7647	Intermediate Similarity	NPC471450
0.7647	Intermediate Similarity	NPC160583
0.7642	Intermediate Similarity	NPC114188
0.764	Intermediate Similarity	NPC477817
0.764	Intermediate Similarity	NPC167037
0.764	Intermediate Similarity	NPC477819
0.764	Intermediate Similarity	NPC285761
0.764	Intermediate Similarity	NPC6978
0.764	Intermediate Similarity	NPC244385
0.764	Intermediate Similarity	NPC138621
0.7634	Intermediate Similarity	NPC474189
0.7634	Intermediate Similarity	NPC318390
0.7634	Intermediate Similarity	NPC474349
0.7629	Intermediate Similarity	NPC470923
0.7624	Intermediate Similarity	NPC73385
0.7624	Intermediate Similarity	NPC470434
0.7624	Intermediate Similarity	NPC470168
0.7624	Intermediate Similarity	NPC267510
0.7624	Intermediate Similarity	NPC31346
0.7619	Intermediate Similarity	NPC125361
0.7619	Intermediate Similarity	NPC51925
0.7619	Intermediate Similarity	NPC472901
0.7619	Intermediate Similarity	NPC306131
0.7619	Intermediate Similarity	NPC43976

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 NPC94127 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	162
0.1-0.2	1898
0.2-0.3	4378
0.3-0.4	1929
0.4-0.5	358
0.5-0.6	186
0.6-0.7	185
0.7-0.8	54
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
0.7865	Intermediate Similarity	NPD7525	Registered
0.7545	Intermediate Similarity	NPD7327	Approved
0.7545	Intermediate Similarity	NPD7328	Approved
0.7527	Intermediate Similarity	NPD7338	Clinical (unspecified phase)
0.7477	Intermediate Similarity	NPD7516	Approved
0.7419	Intermediate Similarity	NPD6695	Phase 3
0.7264	Intermediate Similarity	NPD6412	Phase 2
0.7257	Intermediate Similarity	NPD8294	Approved
0.7257	Intermediate Similarity	NPD8377	Approved
0.7222	Intermediate Similarity	NPD3701	Clinical (unspecified phase)
0.7193	Intermediate Similarity	NPD8335	Approved
0.7193	Intermediate Similarity	NPD8033	Approved
0.7193	Intermediate Similarity	NPD8380	Approved
0.7193	Intermediate Similarity	NPD8378	Approved
0.7193	Intermediate Similarity	NPD8296	Approved
0.7193	Intermediate Similarity	NPD8379	Approved
0.7191	Intermediate Similarity	NPD6926	Approved
0.7191	Intermediate Similarity	NPD6924	Approved
0.7113	Intermediate Similarity	NPD4751	Clinical (unspecified phase)
0.7113	Intermediate Similarity	NPD7750	Discontinued
0.7113	Intermediate Similarity	NPD7524	Approved
0.7111	Intermediate Similarity	NPD7339	Approved
0.7111	Intermediate Similarity	NPD6942	Approved
0.7097	Intermediate Similarity	NPD6930	Phase 2
0.7097	Intermediate Similarity	NPD6931	Approved
0.7087	Intermediate Similarity	NPD7638	Approved
0.7043	Intermediate Similarity	NPD7503	Approved
0.7033	Intermediate Similarity	NPD6933	Approved
0.7019	Intermediate Similarity	NPD7639	Approved
0.7019	Intermediate Similarity	NPD7640	Approved
0.7009	Intermediate Similarity	NPD5739	Approved
0.7009	Intermediate Similarity	NPD6402	Approved
0.7009	Intermediate Similarity	NPD6675	Approved
0.7009	Intermediate Similarity	NPD7128	Approved
0.6989	Remote Similarity	NPD6929	Approved
0.6983	Remote Similarity	NPD6370	Approved
0.6966	Remote Similarity	NPD4243	Approved
0.6957	Remote Similarity	NPD6932	Approved
0.6949	Remote Similarity	NPD7507	Approved
0.6937	Remote Similarity	NPD6882	Approved
0.6931	Remote Similarity	NPD4202	Approved
0.6915	Remote Similarity	NPD7509	Discontinued
0.6915	Remote Similarity	NPD6928	Phase 2
0.6915	Remote Similarity	NPD4748	Discontinued
0.6881	Remote Similarity	NPD6899	Approved
0.6881	Remote Similarity	NPD7320	Approved
0.6881	Remote Similarity	NPD6881	Approved
0.6832	Remote Similarity	NPD7087	Discontinued
0.6827	Remote Similarity	NPD4755	Approved
0.6818	Remote Similarity	NPD6373	Approved
0.6818	Remote Similarity	NPD6372	Approved
0.6813	Remote Similarity	NPD4785	Approved
0.6813	Remote Similarity	NPD4784	Approved
0.681	Remote Similarity	NPD6054	Approved
0.681	Remote Similarity	NPD6059	Approved
0.6809	Remote Similarity	NPD7645	Phase 2
0.6809	Remote Similarity	NPD6683	Phase 2
0.6789	Remote Similarity	NPD5701	Approved
0.6789	Remote Similarity	NPD5697	Approved
0.6778	Remote Similarity	NPD7152	Approved
0.6778	Remote Similarity	NPD7151	Approved
0.6778	Remote Similarity	NPD7150	Approved
0.6777	Remote Similarity	NPD7319	Approved
0.6774	Remote Similarity	NPD5776	Phase 2
0.6774	Remote Similarity	NPD6925	Approved
0.6765	Remote Similarity	NPD6399	Phase 3
0.6757	Remote Similarity	NPD7290	Approved
0.6757	Remote Similarity	NPD6883	Approved
0.6757	Remote Similarity	NPD7102	Approved
0.675	Remote Similarity	NPD8293	Discontinued
0.6742	Remote Similarity	NPD6922	Approved
0.6742	Remote Similarity	NPD6923	Approved
0.6737	Remote Similarity	NPD7514	Phase 3
0.6735	Remote Similarity	NPD6893	Approved
0.6727	Remote Similarity	NPD6011	Approved
0.6702	Remote Similarity	NPD7145	Approved
0.6698	Remote Similarity	NPD5285	Approved
0.6698	Remote Similarity	NPD5286	Approved
0.6698	Remote Similarity	NPD4700	Approved
0.6698	Remote Similarity	NPD4696	Approved
0.6696	Remote Similarity	NPD8130	Phase 1
0.6696	Remote Similarity	NPD6847	Approved
0.6696	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6696	Remote Similarity	NPD6617	Approved
0.6696	Remote Similarity	NPD6649	Approved
0.6696	Remote Similarity	NPD6650	Approved
0.6696	Remote Similarity	NPD6009	Approved
0.6696	Remote Similarity	NPD6869	Approved
0.6694	Remote Similarity	NPD7736	Approved
0.6667	Remote Similarity	NPD6083	Phase 2
0.6667	Remote Similarity	NPD6013	Approved
0.6667	Remote Similarity	NPD6012	Approved
0.6667	Remote Similarity	NPD6084	Phase 2
0.6667	Remote Similarity	NPD6014	Approved
0.6667	Remote Similarity	NPD7144	Approved
0.6667	Remote Similarity	NPD7143	Approved
0.6639	Remote Similarity	NPD6067	Discontinued
0.6637	Remote Similarity	NPD8297	Approved
0.6636	Remote Similarity	NPD5223	Approved
0.6634	Remote Similarity	NPD6051	Approved
0.6634	Remote Similarity	NPD5328	Approved
0.6633	Remote Similarity	NPD4786	Approved
0.661	Remote Similarity	NPD6015	Approved
0.661	Remote Similarity	NPD6016	Approved
0.6602	Remote Similarity	NPD8171	Discontinued
0.6583	Remote Similarity	NPD7492	Approved
0.6579	Remote Similarity	NPD4632	Approved
0.6579	Remote Similarity	NPD8133	Approved
0.6577	Remote Similarity	NPD6686	Approved
0.6574	Remote Similarity	NPD4633	Approved
0.6574	Remote Similarity	NPD5225	Approved
0.6574	Remote Similarity	NPD5224	Approved
0.6574	Remote Similarity	NPD5226	Approved
0.6574	Remote Similarity	NPD5211	Phase 2
0.6569	Remote Similarity	NPD3168	Discontinued
0.6562	Remote Similarity	NPD7332	Phase 2
0.6559	Remote Similarity	NPD4190	Phase 3
0.6559	Remote Similarity	NPD5275	Approved
0.6555	Remote Similarity	NPD5988	Approved
0.6545	Remote Similarity	NPD6008	Approved
0.6529	Remote Similarity	NPD6616	Approved
0.6514	Remote Similarity	NPD4754	Approved
0.6514	Remote Similarity	NPD5175	Approved
0.6514	Remote Similarity	NPD5174	Approved
0.6505	Remote Similarity	NPD8034	Phase 2
0.6505	Remote Similarity	NPD8035	Phase 2
0.6505	Remote Similarity	NPD6079	Approved
0.6505	Remote Similarity	NPD7637	Suspended
0.65	Remote Similarity	NPD3618	Phase 1
0.6495	Remote Similarity	NPD6898	Phase 1
0.6495	Remote Similarity	NPD6902	Approved
0.6476	Remote Similarity	NPD5695	Phase 3
0.6475	Remote Similarity	NPD7078	Approved
0.6471	Remote Similarity	NPD4753	Phase 2
0.6465	Remote Similarity	NPD3665	Phase 1
0.6465	Remote Similarity	NPD3133	Approved
0.6465	Remote Similarity	NPD3666	Approved
0.646	Remote Similarity	NPD4634	Approved
0.6458	Remote Similarity	NPD4195	Approved
0.6455	Remote Similarity	NPD5141	Approved
0.6429	Remote Similarity	NPD3667	Approved
0.6423	Remote Similarity	NPD6033	Approved
0.6422	Remote Similarity	NPD7632	Discontinued
0.64	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6396	Remote Similarity	NPD4767	Approved
0.6396	Remote Similarity	NPD4768	Approved
0.6387	Remote Similarity	NPD6319	Approved
0.6372	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6364	Remote Similarity	NPD7604	Phase 2
0.6356	Remote Similarity	NPD6335	Approved
0.6354	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.6337	Remote Similarity	NPD7521	Approved
0.6337	Remote Similarity	NPD6684	Approved
0.6337	Remote Similarity	NPD5330	Approved
0.6337	Remote Similarity	NPD7334	Approved
0.6337	Remote Similarity	NPD7146	Approved
0.6337	Remote Similarity	NPD6409	Approved
0.6333	Remote Similarity	NPD5983	Phase 2
0.6325	Remote Similarity	NPD6274	Approved
0.6321	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6303	Remote Similarity	NPD7100	Approved
0.6303	Remote Similarity	NPD7101	Approved
0.6296	Remote Similarity	NPD5696	Approved
0.6283	Remote Similarity	NPD5128	Approved
0.6283	Remote Similarity	NPD4729	Approved
0.6283	Remote Similarity	NPD4730	Approved
0.6277	Remote Similarity	NPD1810	Approved
0.6277	Remote Similarity	NPD1811	Approved
0.6271	Remote Similarity	NPD6317	Approved
0.6263	Remote Similarity	NPD4221	Approved
0.6263	Remote Similarity	NPD4223	Phase 3
0.6262	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6262	Remote Similarity	NPD5222	Approved
0.6262	Remote Similarity	NPD4697	Phase 3
0.6262	Remote Similarity	NPD5221	Approved
0.626	Remote Similarity	NPD6336	Discontinued
0.6238	Remote Similarity	NPD5329	Approved
0.6238	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6226	Remote Similarity	NPD7748	Approved
0.622	Remote Similarity	NPD8449	Approved
0.6218	Remote Similarity	NPD6314	Approved
0.6218	Remote Similarity	NPD6313	Approved
0.6214	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6214	Remote Similarity	NPD6903	Approved
0.6211	Remote Similarity	NPD8264	Approved
0.6207	Remote Similarity	NPD6053	Discontinued
0.6204	Remote Similarity	NPD7902	Approved
0.6204	Remote Similarity	NPD5173	Approved
0.62	Remote Similarity	NPD4788	Approved
0.6198	Remote Similarity	NPD6909	Approved
0.6198	Remote Similarity	NPD6908	Approved
0.6196	Remote Similarity	NPD4267	Clinical (unspecified phase)
0.619	Remote Similarity	NPD5281	Approved
0.619	Remote Similarity	NPD5284	Approved
0.619	Remote Similarity	NPD7515	Phase 2
0.6182	Remote Similarity	NPD5344	Discontinued
0.6176	Remote Similarity	NPD5279	Phase 3
0.6176	Remote Similarity	NPD6098	Approved
0.6174	Remote Similarity	NPD5169	Approved
0.6174	Remote Similarity	NPD5251	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