NPASS Compound

Natural Product: NPC321916

Natural Product ID	NPC321916
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Diinsinin
IUPAC Name	n.a.
Synonyms	diinsinin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL447954
PubChem CID	10676233
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 83 90 0 0 0 0 0 0 0 0999 V2000 6.2851 -1.7719 -3.9009 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9708 -0.8258 -3.1608 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5611 -0.8210 -1.7095 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2255 -0.5468 -1.5666 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8243 -0.3587 -0.2554 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6447 -1.0727 -0.0820 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3740 -0.5911 0.1763 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3111 -1.4904 0.3176 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0289 -1.0703 0.5742 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0032 -2.0037 0.7094 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3142 0.2676 0.7129 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7301 1.1532 0.5747 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0436 0.7316 0.3123 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4998 2.5329 0.6972 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8548 2.9503 0.6592 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6801 2.0992 1.6202 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7121 0.6886 0.9903 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5521 0.8488 -0.2107 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2958 1.9215 -1.0342 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2805 2.7610 -0.6745 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0677 2.1116 -2.1844 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0842 1.2369 -2.5038 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3443 0.1588 -1.6775 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5579 -0.0210 -0.5206 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8548 -1.1145 0.2823 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4116 -2.2566 -0.3414 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7428 -1.8060 -0.9339 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4086 -0.7953 -1.9693 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9856 -0.7098 -3.0830 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5587 -3.3904 0.5850 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1798 -4.6591 0.1996 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3073 -5.7490 1.0567 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8185 -5.5911 2.3214 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1995 -4.3274 2.7146 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0709 -3.2344 1.8533 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9527 -6.6814 3.1958 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8784 1.3746 -3.6265 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9983 4.3875 0.9629 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9794 5.1561 0.3872 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1322 6.4980 0.6555 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2607 7.0887 1.5399 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2553 6.3503 2.1442 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1342 4.9895 1.8446 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6245 6.9421 3.0355 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3354 8.4497 1.8774 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8068 -0.8165 0.7754 C 0 0 1 0 0 0 0 0 0 0 0 0 6.6176 -2.0113 0.3944 C 0 0 2 0 0 0 0 0 0 0 0 0 6.7664 -2.2074 -1.0836 C 0 0 2 0 0 0 0 0 0 0 0 0 8.0113 -2.7157 -1.3628 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0528 -3.1931 0.9088 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6767 0.2395 1.0465 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3092 -1.6828 -3.6984 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0646 -1.0266 -3.1979 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8367 0.2068 -3.5367 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2409 -0.1301 -1.1868 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6129 0.7222 -0.1540 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5614 -2.5523 0.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8213 -2.7506 1.3759 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8280 1.4843 0.2135 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6964 2.5158 1.6617 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1670 2.0569 2.5962 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1906 0.0535 1.7664 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8724 2.9466 -2.8310 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7919 -2.5643 -1.2331 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3229 -1.3653 -0.1065 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2725 -2.6685 -1.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7753 -4.7687 -0.8087 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0072 -6.7394 0.7453 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6012 -4.2200 3.7166 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3706 -2.2663 2.1744 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6353 -7.5807 2.8789 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6907 0.8174 -4.4694 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6824 4.6993 -0.3207 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8963 7.1062 0.2099 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6661 4.4453 2.3386 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5410 7.2248 2.6674 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3303 9.1481 1.1669 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2861 -1.0415 1.7296 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6366 -1.9545 0.8311 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9559 -2.8570 -1.4875 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9553 -3.6970 -1.5853 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3694 -3.3957 1.8183 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4167 0.7285 1.8707 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 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 9 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 26 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 33 36 1 0 22 37 1 0 15 38 1 1 38 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 42 44 1 0 41 45 1 0 5 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 47 50 1 0 46 51 1 0 48 3 1 0 13 7 1 0 20 15 1 0 28 23 1 0 35 30 1 0 43 38 1 0 17 11 1 0 24 18 1 0 1 52 1 0 2 53 1 0 2 54 1 0 3 55 1 1 5 56 1 6 8 57 1 0 10 58 1 0 13 59 1 0 16 60 1 0 16 61 1 0 17 62 1 1 21 63 1 0 26 64 1 6 27 65 1 0 27 66 1 0 31 67 1 0 32 68 1 0 34 69 1 0 35 70 1 0 36 71 1 0 37 72 1 0 39 73 1 0 40 74 1 0 43 75 1 0 44 76 1 0 45 77 1 0 46 78 1 1 47 79 1 1 48 80 1 6 49 81 1 0 50 82 1 0 51 83 1 0 M END

Standard InCHIKey	FTKAVFCYTQUGTN-BNDLDUQUSA-N
Standard InCHI	InChI=1S/C36H32O15/c37-13-27-31(44)32(45)33(46)35(49-27)47-17-8-21(41)28-18-12-36(50-25(28)9-17,15-3-6-19(39)20(40)7-15)51-26-11-23(43)30-22(42)10-24(48-34(30)29(18)26)14-1-4-16(38)5-2-14/h1-9,11,18,24,27,31-33,35,37-41,43-46H,10,12-13H2/t18-,24-,27-,31-,32+,33-,35-,36-/m1/s1
SMILES	OC[C@H]1O[C@@H](Oc2cc(O)c3c(c2)O[C@@]2(C[C@H]3c3c(O2)cc(c2c3O[C@H](CC2=O)c2ccc(cc2)O)O)c2ccc(c(c2)O)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	704.17	Volume:	660.34 ? Van der Waals volume.
Dense:	1.066	LogP:	1.712 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.711 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.8 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	44.0
TPSA:	245.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	9.0	Rings:	8.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.135	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.865	Fsp³:	0.306
MCE-18:	167.851 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.877	Fluc inhibitor:	0.218 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.799 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.961 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.178	Promiscuous compounds:	0.178

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.733	MDCK Permeability:	-5.022
Pgp-inhibitor:	0.0	Pgp-substrate:	0.707
PAMPA:	0.77 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.193	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.853
Plasma Protein Binding (PPB):	88.917%	Volume Distribution (VD):	-0.039
Fu:	10.205% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.948
BSEP inhibitor:	0.012

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.07
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.028
HLM stability:	0.002 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

3.017

Half-life (T1/2):

4.926

ADMET: Toxicity

hERG Blockers:	0.125	hERG Blockers (10um):	0.345
Human Hepatotoxicity (H-HT):	0.978	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.958	Rat Oral Acute Toxicity:	0.436
Maximum Recommended Daily Dose:	0.914	Skin Sensitization:	1.0
Carcinogencity:	0.098	Eye Corrosion:	0.0
Eye Irritation:	0.006	Respiratory Toxicity:	0.111
Drug-induced Neurotoxicity:	0.027	Ototoxicity:	0.996
Hematotoxicity:	0.089	Drug-induced Nephrotoxicity:	0.949
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.248
A549 Cytotoxicity:	1.0	Hek293 Cytotoxicity:	0.982
BCF:	0.749 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.543 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.254 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.413 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO30500	Sarcophyte piriei	Species	Balanophoraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8786365]
NPO30500	Sarcophyte piriei	Species	Balanophoraceae	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	2

Activity Type	# Activity
Others	2

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
NPT2	Others	Unspecified	n.a.	IC50	=	13140.0	nM	PMID[8786365]
NPT2	Others	Unspecified	n.a.	IC50	=	39000.0	nM	PMID[8786365]

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 NPC321916 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	21870
0.1-0.2	24286
0.2-0.3	3037
0.3-0.4	591
0.4-0.5	53
0.5-0.6	14
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9318	High Similarity	NPC318119
0.6517	Remote Similarity	NPC39351
0.6374	Remote Similarity	NPC29830
0.5699	Remote Similarity	NPC97052
0.5638	Remote Similarity	NPC219163
0.5532	Remote Similarity	NPC163191
0.5524	Remote Similarity	NPC168789
0.551	Remote Similarity	NPC236934
0.5426	Remote Similarity	NPC169248
0.5426	Remote Similarity	NPC72649
0.5417	Remote Similarity	NPC206378
0.5357	Remote Similarity	NPC483821
0.5312	Remote Similarity	NPC471457
0.5243	Remote Similarity	NPC105283
0.5204	Remote Similarity	NPC181014
0.5155	Remote Similarity	NPC26195
0.5052	Remote Similarity	NPC170475

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC321916 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5714
0.1-0.2	3391
0.2-0.3	37
0.3-0.4	7
0.4-0.5	1
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